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SUMMARY Lactating female rats are known to exhibit a reduced or 'buffered' plasma corticosterone response to stress. The depressed response is a post-partum phenomenon seen only in the lactating rat with pups, since a lactating rat whose pups have been removed for 8 days gives a normal response to ether stress. Thus it appears that lactation may be necessary for a reduced response to stress, and the reappearance of the normal response coincides with the time when the animal resumes its oestrous cycle. Maternal behaviour by itself could be ruled out as a causative factor since a normal adrenal response was seen in virgin rats which had been sensitized to pups. A depressed corticosteroid response to ether stress was obtained after ovariectomy or treatment with prolactin (2 mg/day for 5 days). However, the effect of ovariectomy on plasma corticosterone levels after ether stress could be reversed by the injection of 5 μg oestradiol benzoate daily for 5 days. The minimum effective dose of dexamethasone phosphate that was necessary to prevent increased plasma corticosterone levels after ether stress in the normal female rat was 400 μg/100 g body weight whereas a lactating rat required only 6·25 μg and a virgin rat treated with prolactin required 25 μg. It is apparent that prolactin is acting, in part at least, to increase the sensitivity of the negative feedback system.

RELAXIN, a water-soluble, physiologically active substance of the ovary has been prepared in partly purified form by two different methods. Fevold, Hisaw, and Meyer (1932) extracted fresh sow corpora lutea with acid alcohol and worked up the active material by solution in and precipitation from organic solvents. The activity of the final product, prepared as an iso-electric precipitate at pH 5.4, was 30 units per mg. Using semi-dried, defatted luteal tissue obtained as a by-product from a commercial procedure for the preparation of progestin, Albert, Money, and Zarrow (1946) prepared relaxin with approximately the same order of activity by differential solubility in water, ammonium sulfate solutions and cold dilute alcohol.

ACOMPLETE understanding of the role of progesterone in pregnancy has been handicapped in the past by the lack of sensitive assay that could be used on small amounts of blood. Pregnanediol determinations are of limited significance since they measure the degradation products of progesterone and steroids of a similar nature and also reflect not only the level of the hormone in the blood but also variations in the metabolism of the hormone. Early attempts to measure the progestin level of the blood in women (Clauberg, Thiel and Ziecker, 1933; Block, 1936) and pregnant rabbits (Block, 1936) failed to reveal any activity. Block reported the presence of less than 1 rabbit unit in 12 liters of blood obtained from pregnant sows. The use of the rabbit-intrauterine test revealed the presence of progestin in the blood of human beings during pregnancy (Haskins, 1941; Hoffmann and von Lam, 1948) however the results were extremely variable.

Pheromonal facilitation of PMS-induced ovulation was compared in six strains of immature mice following exposure to adult males of the same strain. All mice were injected with PMS at 24 days of age and exposed to adult males 51 hr later. Examination of the animals for ovulation was carried out at 72-74 hr after the PMS injection. Significant facilitation of average number of ova released and/or percentage of mice ovulating was found for the BALB/cJ, SWR/J, and C3HeB/FeJ mice at both a dosage of 3 and 7 IU of PMS. The SJL/J strain showed facilitation at the 7 IU dose of PMS, but none at the 3 lU dose. The DBA/2J strain showed an inhibition at 3 1U PMS and facilitation at 7 lU while the C57BL/6J showed no facilitation at either 1, 3, or 7 IU of PMS but did so at S IU. It is apparent a significant strain difference exists both in the ovulatory response of mice to PMS and in the ovulatory response to the combined treatment of PMS and exposure to the adult male of the same strain.

The effects of ACTH and exposure to cold on the concentration of adrenal ascorbic acid and cholesterol were studied in several species. Exposure to severe cold produced significant depression of adrenal ascorbic acid in opossums and dogs, but failed to do so in frogs, toads, chickens, mice, hamsters, rabbits, and cats. ACTH failed to produce such a depletion in frogs, toads, chickens, rabbits, cats, or dogs; significant depressions were observed in opossums, mice and hamsters. Adrenal cholesterol concentrations remained unchanged in most species tested, however, increases were observed in rabbits, following cold exposure, and in frogs, following ACTH treatment.

PMS-induced ovulation in immature rats involves a neuroendocrine pathway. Bilateral electrolytic lesions located in the medial preoptic area, basal-medial preoptic area, or ventral medial anterior hypothalamic area prevented the ovulatory response following a single injection of PMS (pregnant mare's serum). Lesions of the medial preoptic area failed to interfere with ovulation following treatment with PMS and HCG (human chorionic gonadotropin). Electrode placement (sham) into the medial preoptic area failed to alter PMS-induced ovulation. PMS-induced ovulation occurred in the presence of bilateral lesions located in other areas of the hypothalamus than those listed above. From these experiments it is concluded that the mechanism of PMS-induced ovulation involves the medial preoptic and basal anterior hypothalamic regions. (Endocrinology 77: 255, 1965)

Some effects of the maternal environment upon several behaviour patterns of weanling and adult C57BL/10J mice and Purdue Swiss-Albino mice were studied by comparing: i) mice reared by rat mothers, 2) mice reared by their natural mouse mothers in the presence of a rat aunt, and 3) cross-fostered control mice. The rat-mother and rat-aunt preparations both were found to produce measurable, and similar, effects upon the behaviour of weanling and adult mice. Experiment I: C57BL/10J Mice Infantile mortality. A higher mortality was recorded for rat-reared mice and mice reared in the presence of a rat aunt than for mouse-reared mice. Body weight. At weaning, rat-reared mice were heavier than mouse-reared mice or mice reared in the presence of a rat aunt. However, at 63 days of age, rat-reared mice weighed less than mice in either of the other two groups. Open-field behaviour. On the first day of open-field testing, both at 21 days and at 63 days of age, mouse-reared mice were more active than rat-reared mice or mice reared with rat aunts. On Days 2-4 in adulthood control mice defecated less than experimental mice in either of the two groups. Passive avoidance learning. At 21 and 63 days of age, control mice reached criterion sooner than rat-reared mice or mice reared with a rat aunt. Fighting behaviour. More fighting was found among mouse-reared mice than among rat-reared mice or mice reared in the presence of a rat aunt. Experiment 2: Swiss-Albino Mice Infantile mortality. A higher mortality rate was recorded for rat-reared mice and mice reared in the company of a rat aunt than for mouse-reared mice. Body weight. At weaning, subjects in the three treatment groups did not differ significantly from one another in body weight. However, at 63 days of age, rat-reared mice were heavier than mice in either of the other two groups. Open-field behaviour. On the first day of open-field testing, both at 21 days and at 63 days of age, mouse-reared mice were more active than rat-reared mice or mice reared with rat aunts. Control mice were also more active than rat-tended mice on Days 2-4 of open-field testing at weaning. Rat-reared mice defecated more than mouse-reared mice and rat-aunt tended mice on all four days of open-field testing at 21 days of age. However, rat-reared mice defecated less than mice in the other two groups during the four days of adult open-field testing. On Days 2-4 in adulthood, rat-reared mice had a longer latency to leave the starting square than mouse-reared mice or rat-aunt tended mice. Passive avoidance learning. At 21 days and at 63 days of age, control mice reached criterion sooner and achieved a greater number of correct trials than rat-reared mice or mice reared with a rat aunt. Fighting behaviour. No differences in fighting behaviour were found between the three groups of animals used in the experiment.

was postulated that this system existed as a single gene (Chapman & Whitten, 1968), the following experiments were conducted to determine the heritability of the male pheromonal system involved in pmsg-induced facilitation of ovulation. Female mice of the C57BL/6J and SWR/J strains were housed, one per cage, following weaning at 21 days of age. Lighting was kept on a 12 hr on/12 hr off schedule (on at 06.00, off at 18.00 hours). At 09.00 hours on the 24th day of age, each mouse was injected subcutaneously with 2 i.u. pmsg (Ayerst-Equinex). It had previously been shown that this dose of pmsg did not cause ovulation at 24 hr in these strains of mice (Christenson & Eleftheriou, 1972). At noon on the 2nd day (51 hr later), each female was transferred to a cage with a double wire partition. The female was housed on the side which the male had used previously and the male was transferred to the opposite side. All females were killed approximately 21 hr later, i.e. 72 to 74 hr after pmsg injection, and the oviducts were removed for examination under a dissecting microscope at 40 magnification. Ova were counted and the state of the ova, i.e. whether clumped, denuded, etc. (Zarrow, Caldwell, Hafez & Pincus, 1958), was recorded. Eighteen females of strain C57BL/6J were exposed to C57BL/6J males and another eighteen females were exposed to SWR/J males. Similarly, eighteen females of strain SWR/J were exposed to C57BL/6J and eighteen to SWR/J males. For controls, another eighteen females of each strain were injected with pmsg, and transferred to a clean cage but were not exposed to a male, while a further eighteen females were injected with saline alone and also were not

Three types of staircase phenomena were observed in vitro in the pregnant and post partum rat myometrium by varying the frequency of electrical stimulation. A positive staircase (positive correlation between frequency of stimulation and amount of tension developed) was occasionally observed on day 1 of pregnancy. This response rapidly changed to a transient and then to a negative staircase within a few hours. The negative staircase was observed throughout the remainder of pregnancy and for the first few hours following parturition. At approximately 8–12 hours post partumi.e the predominant type of staircase was of the transient type which changed to the positive type at about 24 hours post partum. A few positive staircase responses were recorded on day 19 of pregnancy, i.e. as early as three days prior to parturition. Uteri of ovariectomized rats treated with estrogen, or estrogen and progesterone, showed only the negative type of staircase.

INTRODUCTION IT WAS reported in a previous publication (1) that 17-α-hydroxyprogesterone is 60 times more potent than progesterone as measured by the Hooker-Forbes bioassay in the mouse. In the rabbit, however, Junkmann found that the free compound was inactive (2). As there appeared to be a species difference, and as the addition of the hydroxyl group to the 17 position of other steroids of low potency increases their activity, it was of interest to extend this study to include the rabbit and the human being. The progestational reaction in the rabbit has been accepted as the biological criterion for this class of compounds since progesterone was first isolated, and use in human therapy is one of the most practical goals in the study of progestational compounds. Recently, 17-α-hydroxyprogesterone and its caproate ester have gained attention by clinical use. Junkmann (2) found that the caproate ester of 17-α-hydroxyprogesterone, but not the free compound, had prolonged action in the rabbit. Davis and Wied ...

SummaryIt was demonstrated that the plasma corticosterone response to ACTH is extremely weak in the 7-day-old rat. The present results indicate that pretreatment with 2 IU of ACTH in a beeswax-oil suspension on day 5 of age resulted in a 7-day-old rat that is capable of responding to ACTH in a manner comparable to that seen in younger and older rats. It is concluded from these studies that the “biphasic pattern” seen in the neonatal rat (characterized by a depressed adrenal response at day 7) is due to a depressed ability of the adrenal cortex to respond to ACTH. The hypothesis is presented that the depressed ability of the adrenal cortex to respond is the result of a relative lack in circulating ACTH. It is suggested that decreased ACTH secretion is the result of a failure of CRF to get to the pituitary because the hypothalamic-pituitary system is not complete in the 7-day-old rat.

Advancement of the time of PMSinduced ovulation in immature Purdue Wistar rats was produced by treatment with 0.2–2 mg progesterone (P). Medroxyprogesterone and norethindrone were effective but other steroids, including some with progestational activity, were not. The induction of ovulation by P does not seem to be due to altered ovarian sensitivity to LH. In rats hypophysectomized 22-24 hr after PMS treatment, an 80 μg dose of LH appeared to be equally effective when given to Ptreated and control rats 30 hr after a PMS injection. P can advance ovulation if given 19-32 hr after PMS, but not at 34 hr. Administration of P at 19 hr after PMS treatment seemed to alter the duration of the period during which pentobarbital (PBTL) treatment can prevent ovulation. In such rats the colony period for LH release appeared to begin 5 hr sooner than in rats given P 24 hr after PMS, although it terminated at the same time. This suggested that the onset of the colony period for LH release shifted to an earlier time, and ...

There is considerable contradiction in the literature regarding the influence of antithyroidal drugs on the adrenal cortex. Kennedy and Purvis (1941) reported adrenal hypertrophy after feeding Brassica seed, while Richter and Clisby (1942), Williams, Bissell, Jandorf, and Peters (1944), and Gordon, Goldsmith and Charipper (1944) found no effect on adrenal size. Others have expressed the opinion that any change in the weight of the adrenal gland is concurrent with a loss in body weight and have reported that if the weight of the adrenal gland is expressed as a percentage of body weight no effect is apparent (Leblond and Hoff, 1944; Williams, Weinglass, Bissell and Peters, 1944; Leathern, 1945 and 1946; Smithcors, 1945). Finally, a third group of investigators have reported a significant involution of the adrenal glands as the result of treatment with the goitrogens (Bauman and Marine, 1945; McQuillan and Trikojus, 1946; Deane and Greep, 1947), and have found hemorrhage and necrosis in the adrenal cortex

Summary. Two types of nest building are found in the rabbit. One type of nest is made of straw or similar elements available to the animal, and a second type of nest is composed of straw into which hair is in¬ corporated after being plucked from the body. The second type of nest is called a maternal nest and is considered to be part of the maternal behaviour complex. Maternal-nest building was induced in 209 out of 250 (84 %) rabbits following complete removal of the entire conceptus mass on Days 20 to 27 of gestation, as compared with a 96 % maternalnest-building rate in 941 control rabbits from the same colony. The maternal-nest-building behaviour was also induced in twelve out of sixteen (75 %) rabbits following ovariectomy on Days 20 to 24 of gestation and in five out of eleven rabbits made pseudopregnant with human chorionic gonadotrophin (hcg). Comparable results were obtained in a separate study that used the Dutch-belted rabbit, although a higher percentage of animals in this race built maternal nests following pseudopregnancy or ovariectomy during gestation. Treatment with stilboestrol, progesterone and prolactin induced maternal-nest building in four out of seventeen rabbits and lactation in all the animals. Possible endocrine mechanisms involved are discussed.

Female New Zealand White rabbits mated to Purdue-Dutch belted males were treated with testosterone propionate from Day 17–29 of gestation. While there was no apparent effect on gestation and maternal behaviors of injected mothers, the hybrid offspring showed anatomical and behavioral masculinization. Adult hybrid offspring were gonadectomized and treated with estradiol and progesterone to induce nest-building behavior. Ninety per cent of the control females built maternal nests as compared to only 11% of the female offspring of mothers treated with high levels of testosterone during gestation. None of the control males built maternal nests. Testosterone propionate apparently influences the organization of CNS structures mediating maternal-nest building in the adult rabbit. The similarity of these results to the findings concerned with the role of the androgen in the development of sexual behavior are discussed.

Removal of the olfactory bulbs in pregnant and non-pregnant mice has been shown to lead to a loss ofmaternal behaviour (Gandelman, Zarrow, Denenberg & Myers, 1971). Cannibalism of the young occurs in practically all cases, and in the few instances when cannibalism does not take place, the young invariably die from neglect. In mice, therefore, the olfactory system must be functional for maternal behaviour to occur. By contrast, data obtained from the rat indicate that no one sensory system is necessary for the exhibition of maternal behaviour (Beach & Jaynes, 1956). In our original experiment (Gandelman, Zarrow, Denenberg & Myers, 1971), multiparous mice were bulbectomized on Day 12 ofgestation, allowed to litter, and were killed immediately after the death of their young in order to verify the brain lesions. It was not known, therefore, whether multiple experiences with pregnancy and parturition occurring subsequent to olfactory bulb removal could overcome the debilitating effect of the lack of olfaction upon maternal behaviour, or whether another sensory system might eventually assume the role originally played by the olfactory system. The present experiment inves¬ tigated this hypothesis. Twelve, 60-day-old, nulliparous mice of the Rockland-Swiss albino strain had both olfactory bulbs removed. The operation consisted of drilling a 2-mm hole in the skull over the bulbs and removing the tissue by aspiration. The animals were then housed individually in 5 7 11 in. translucent cages and allowed free access to food and water. Since it has been shown that sham operations do not affect maternal behaviour in 'mice (Gandelman, Zarrow, Denenberg & Myers, 1971; Zarrow, Gandelman & Denenberg, 1971), such controls were not employed. Five days after surgery, one adult male Rockland-Swiss albino mouse was placed into each cage and the females were checked every morning for the presence of a vaginal plug. After a plug was discovered, the male was removed and the female was left in isolation throughout pregnancy, parturition and the lactation period. During lactation, the females and their young were observed twice a day until the death of the offspring, after which the male was returned to the female's cage. If a vaginal plug was not found within 2 weeks, the male was removed and replaced by another male. If a vaginal plug was not found within 7 days after the second male was introduced, the female was killed and its

WITHIN recent years the domestic bird has been used to an increasing extent in physiologic and endocrinologic studies. Some of these investigations have revealed inherent differences between the bird and the mammal (Jailer and Boas, 1950; Zarrow and Baldini, 1952; Morris, 1953; Newcomer, 1959; Nalbandov, 1953). Recently the advent of many new steroids has led to extensive studies on these compounds in the mammal but little work has been done in the bird. The present investigation is concerned with the effect of some of these compounds in the chick and and is designed to determine whether the differences in the action of these compounds in the chick and rat are of a quantitative or qualitative nature and to determine whether some structure-function relationship can be obtained. MATERIAL AND METHODS The chick oviduct test was carried out on 16-day-old chicks of the White Leghorn strain. All birds were injected intramuscularly for …

INTRODUCTION INVESTIGATIONS on the physiology of relaxin would indicate that it is a hormone of pregnancy (1, 2). Additional evidence for this concept may be obtained also from studies on the presence of this hormone in the blood and other tissues during gestation. The concentration of relaxin in the blood of the rabbit (3) and the guinea pig (4) and in the ovary of the pregnant sow increases progressively during pregnancy until a plateau is reached, and then drops precipitously at parturition. In the human being, however, relaxin has been detected in the first part of pregnancy but not in the last trimester (5, 6). Pommerenke (6) reported a drop in the level of serum relaxin of women in the fifth month of pregnancy and a total absence (at 5–6 ml. of serum) by the eighth month. The present investigation was undertaken to determine quantitatively the blood serum levels of relaxin in women throughout pregnancy and at parturition. In addition, several pregnancies complicated by pre-eclampsia and diabetes wer...

SUMMARY The administration of a high dose of androgen on a single day to a neonatal female rat has been shown repeatedly to induce persistent vaginal cornification (PVC). However, this type of treatment does not parallel the continuous androgen secretion present in the male, and the high doses that have been used could represent a pharmacological and not a physiological effect. Experiments were carried out to determine the minimal effective dose of testosterone propionate (TP) needed to cause PVC when the androgen is administered to the neonatal rat for the first 10 days of life or as a long-acting ester. Injection of 1, 3 or 9 μg TP on days 1–10 of life in female rats induced PVC in adulthood. All three doses were found to be more effective than a testicular transplant on day 1. In female rats injected with low doses of TP twice daily for the first 10 days of life, PVC was shown between 90 and 100 days of life in 21 out of 22 animals given 0·5 μg TP/injection, and in eight out of 22 animals given 0·05 μg TP/injection. In an experiment where female rats were given a single injection of 0·1, 1·0 or 10·0 μg TP, or 0·1 or 1·0 μg testosterone cyclopentylpropionate (TC, a long-acting androgen) on the first day after birth, PVC occurred at 90–100 days of age in 15 of the 18 animals which were injected with 10 μg TP, in none of the 17 animals which were injected with 1 μg TP, and in 10 of 11 animals which were injected with 1 μg TC. The effects of all treatments on vaginal opening, first oestrus, ovarian weight, body weight and sexual behaviour are reported. The use and implications of low dose regimens are discussed in relation to the construction of an experimental model for the study of sexual differentiation.

ConclusionsAndrogen sterilization results in the elimination of the multiphasic dose-response curve obtained with the OCD bio-assay for LH. The dose-response curve in the androgenized animals is highly reproducible, but the sensitivity of the assay is considerably reduced. The abolition of the multiphasic curve by androgen treatment suggests that endogenous LH release is responsible for the multiphasic type of response in the non-androgenized rat. A linear log dose-response relationship for LH is obtained between 0.0625 μg and 0.25 μg using a 5-hour assay time interval, and between 0.25 μg and 1.0 μg using a 7-hour assay time interval. This response is reproducible and is specific for LH.

The ovaiy, uterus and placenta have been suggested as possible sites for the formation of relaxin (Herrick, 1928; Hisaw, 1926, 1929; Hisaw, Zarrow, Money, Talmage and Abramovitz, 1944; Zarrow, 1947, 1948). Not only has it been possible to extract relaxin from these three organs but there is some indication that they may serve as sources of the hormone in the normal economy of the organism. However, this work was carried out on different species so that it is difficult to evaluate the relative role of the various sites in the formation of relaxin in a given species. In the sow, the ovary would appear to be the major source (Hisaw and Zarrow, 1948), whereas the placenta may play a more significant role in the mouse (Newton and Beck, 1939; Hall and Newton, 1947) and the guinea pig (Herrick, 1927; Zarrow, 1948). In view of the many possible sources of relaxin noted among different species

The hybrid offspring of reciprocal crosses between C57BL/10J and Swiss Albino mice were fostered at birth to Swiss Albino mouse mothers or to Purdue-Wistar rat mothers. Measures were taken of incidence of survival, body weight, open-field performance, passive avoidance learning, and fighting. As compared to mice reared by mouse mothers after birth, mice reared by rat mothers (a) had a lower incidence of survival at weaning; (b) weighed more; (c) were less active in the open field, defecated less in the field, and had a greater latency to initiate movement in the field; and (d) had poorer passive learning scores. The findings indicate that the postnatal maternal environment has pervasive effects upon a number of behavioral and morphological characters, but reveal a minimal effect of the prenatal environment. Moreover, they indicate that the absence of differences in fighting scores among the 4 groups may be caused by dominant genes.

Five strains of mice were examined for pheromonal facilitationof HCG-induced ovulation. Significant facilitation of both the percentage of mice ovulating and the average number of ova released was obtained in the SJL/J, the SWR/J and the C3H/HeJ strains. Two of the five strains tested, i.e., the DBA/2J and the C57BL/6J strains, failed to show a pheromonal facilitationof HCG-induced ovulation. An increased number of ova per mouse ovulating also was exhibited in two (SJL/J and C3H/HeJ) of the three strains that showed facilitation.A comparison of the five strains for pheromonal facilitation of either PMSGinduced ovulation (previously reported by us) or HCG-induced ovulation indicates that the three strains (SJL/J, SWR/J, C3H/HeJ), that exhibited facilitation when treated with PMSG, also showed facilitation when treated with HCG.

THE remarkable loosening of the pelvic ligaments which occurs both at the symphysis pubis and iliosacral junctions in the pregnant guinea pig has been observed and described by numerous investigators. These separations become so extensive, as pregnancy progresses, that a condition is attained in which the two halves of the pelvis can be freely and independently manipulated thus making possible an increase in the diameter of the birth canal. Hisaw (1926) found that pronounced relaxation of the pelvis could be induced experimentally by injecting blood serum of pregnant rabbits or guinea pigs into normal virgin guinea pigs during estrus or into castrated female guinea pigs that had been conditioned with estrogen. The pelvic ligaments usually showed marked relaxation within 8 to 12 hours after one injection of the serum. The relaxative substance was found also in the blood of pregnant sows, dogs, cats and mares, in extracts of the placentae of rabbits (Hisaw, 1927, 1929) and corpora lutea of the sow (Hisaw, F...

SummaryBy the use of a precold treatment injection schedule it has been demonstrated that desoxycorticosterone acetate at dose levels of 250 γ and 500 γ and progesterone at 500 γ prolongs the life of adrenalectomized mice subjected to low temperatures. Peanut oil at the dose level of 0.2 cc has been shown to possess a significant toxic action.

The adrenal gland of the neonatal rat is responsive to stress. Three-min exposure at 2 days of age to either heat or electric shock caused a significant increase in plasma corticosterone from a resting level of approximately 11 to 27 μig/100 ml following heat stress and to 16 μig/100 ml following shock. In the 9-day-old rat the corticosterone levels rose from a normal of approximately 6 to 14 μg/100 ml following heat and to 13 μg/100 ml following shock. The time required for maximum response was 30 min in the 2-day-old and 60 min in the 9-day-old rat. Corticosterone levels in the adrenal gland increased in the 9-day-old following either heat or electric shock; however, in the 2-day-old rat only heat was adequate to induce a significant increase in the concentration of corticosterone in the adrenal gland. The increased adrenal response was obtained, when present, in 5 min in both the 2-day-old and the 9-day-old rat. (Endocrinology 79: 631, 1966)

Conclusion1. Thiouracil produces an involution of the adrenal cortex. 2. The atrophic adrenal gland of the thiouracil-treated rat retains its sensitivity to ACTH. 3. It is suggested that the involu...

An in vitro method was employed to measure the dilatability and tensile strength of the uterine cervix of the rat during the estrous cycle, gestation and the puerperium. Dilatability, percent water and cervical weight increased throughout gestation to a maximum at parturition. Tensile strength and percent collagen (as measured by hydroxyproline) of the cervix decreased throughout gestation. Within 48 hours post-partum, all measurements tended to return to values seen in the nonpregnant rat. The maximum dilatability, observed at parturition, was found to be due in part to stretching induced by the fetus traversing the birth canal. Relaxin caused similar changes in dilatability, tensile strengh, percent water and collagen in pregnant ovariectomized rats treated with the ovarian steroids. Measurements obtained in non-pregnant, ovariectomized rats treated with estrogen, progesterone and relaxin yielded comparable results but the magnitude of the cervical dilatability was not as great as that observed in the i...

An analysis was made of more than nine hundred successful parturitions in four strains of rabbits, Oryctolagus cuniculus, for the period, 1953-59. The strains studied were : III, IIIc, AcEp, and X. The results showed that the number of successful pregnancies (production of one or more live-born young) varied from 57 percent in the winter months to 82 percent during the summer. This pattern was significantly different among strains. Within the successful pregnancy group, the proportion of failures to build material nests did not change significantly from season to season or from year to year. The time of nest building was found to differ significantly among the strains.

Litters of four male and two female mice were fostered, at four days of age, to lactating rat mothers whose own litters (two to six days of age) were removed at the time of fostering. Control mouse litters (four males, two females) remained with their natural mothers. Rat-reared mice had a higher mortality rate between birth and weaning but the survivors weighed more at weaning than did mouse-reared mice. Rat-reared mice were less active in an open field on the first day of testing and were less aggressive than mice reared by mouse mothers. The data definitely implicate the mother as a critical determiner of adult behavioral patterns.

Since the discovery by Hisaw (1926) that the separation of the pubic bones in the guinea pig was under the control of a specific substance which was later called relaxin, several controversies have arisen. These controversies are concerned with the identity of this relaxative substance as distinct from the crystalline steroid hormones and with the role played by the steroids in the phenomenon of pubic relaxation. Relaxin was first obtained from the blood of pregnant rabbits (Hisaw, 1926; Brouha and Simmonet, 1928; Tapfer and Haslhofer, 1935; Abramson, Hurwitt and Lesnick, 1937; Marder and Money, 1944). It has also been found in the blood of pregnant sows, dogs, cats, mares and in placentae of rabbits (Hisaw 1927 and 1929), blood of pregnant guinea pigs Hisaw (1927), Zarrow (1947), blood of pregnant women (Pommerenke, 1934; Abramson et al., 1937), and corpora lutea of the sow (Hisaw, 1927; Brouha and Simmonet, 1928; Abramson et al., 1937).

This report compares the effectiveness of various compounds with progestogenic activity in a series of tests involving the chick the rat the mouse and the rabbit. The inhibition of oviduct growth stimulation of decidual growth and the Clauberg test were used for measurement of activity of 17-alpha-hydroxyprogesterone 17-alpha-hydroxyprogesterone caproate 11 dehydroprogesterone 17-alpha-ethyl-19-nortestosterone and 17-alpha-ethinyl-19-nortestosterone. In the chick oviduct test 16-day-old female white Leghorns were treated for 7 days and sacrificed on Day 8. The entire genital tract from the infundibulum to the cloaca was included in the oviduct weight. Injection of stilbestrol alone gave a typical sigmoid dose-response curve with a sharp increase in weight from 13 mg % of body weight at .05 mg daily to 1048 mg percent at 1 mg daily. A standard dose of 1 mg a day of stilbestrol was then selected for further experiments. Progesterone produced a marked inhibition of the stilbestrol-stimulated oviduct in the chick particularly when dissolved in oil; all the compounds tested showed some inhibition ability. Adult female Holtzman rats were castrated treated with 1 mg of estrone for 4 days followed by 9 days of progesterone or one of the test compounds. The uterus was exposed on Day 5 of test-drug treatment and 1 mg of histamine dihydrochloride injected into the left horn. A marked deciduoma was apparent with .5 mg progesterone daily. The degree of deciduomatogenesis was evaluated by comparing the percentage of increase of the histamine-treated horn with the other. At .2-2 mg daily progesterone gave a good dose response curve up to 400% increase when suspended in oil. Suspension of the hormone in saline with "Tween 80" decreased activity by 50%. 11-dehydroprogesterone was twice as effective as progesterone. The other compounds gave little or no response even in large doses. In mice similar tests showed the decidual response in the mouse is a more sensitive index of progestone-like activity than in the rat. No significant activity was observed with any of the test compounds except 17-alpha-ethyl-19-norethisterone. The Clauberg test in rabbits gave similar results to previously reported work. 11-dehydroprogesterone was effective at .15 mg twice the activity of progesterone. It had only a third the activity of progesterone in the Hooker-Forbes test. Both the 17-alpha-ethyl-19-nortestosterone and the 17-alpha-ethinyl-19-nortestosterone appeared to be superior to progesterone in Clauberg and chick-oviduct tests; the ethynyl derivative was superior to the ethyl derviative in the chick test; only 11-dehydroprogesterone mirrored all the activities of progesterone and was consistently superior to the hormone.

Immature rats pretreated with PMS (pregnant mares serum) were studied to determine whether progesterone was present in sufficient amounts and at such a time as to play a role in the release of LH (luteinizing hormone). From no progesterone at PMS injection serum progesterone levels rose to 5.88 plus or minus .28 nonograms per ml. by 56 hours after PMS injection. Ovariectomized and hypophysectomized rats showed undectable and .7 nanograms per ml progesterone respectively following PMS treatment. Progesterone may be one of the signals for the release of LH. The source of progesterone in the immature rat seems to be the ovary and progesterone was secreted by the ovary prior to the formation of the corpora lutea.

SummaryRelaxin is found in the blood of guinea pigs on about the 21st day of pregnancy, at which time relaxation of the symphysis pubis may first be detected by palpation. The concentration of relaxin reaches a peak of 0.5 G.P. units per ml of blood serum on the 28th day and is maintained until the 63rd day when the concentration falls to 0.33 G.P. units per ml. Immediately after parturition a precipitous decline of the relax-in content of the blood serum takes place. The urine shows a concentration of 0.5 G.P. units of relaxin per ml at 42 and 56 days of pregnancy with a drop to 0.25 G.P. units by the 63rd day. The uterus contains about 10 G.P. units per gram of tissue on the 56th and 63rd day of pregnancy whereas the placenta shows 5 G.P. units per gram of tissue on the 56th day and 2.5 G.P. units on the 63rd day. It seems probable that the drop in serum relaxin in the latter part of pregnancy may be due to a decreased output from the placenta.

IT HAS been known for some time that desoxycorticosterone acetate (DCA) possesses weak progestational activity when administered systemically. However, DCA will not bring about progestational changes when applied topically to the endometrium of the rabbit (McGinty, 1942) nor will it cause a positive reaction in the stromal nuclei of the uterus of the mouse following local application (Hooker and Forbes, 1949). Pfiffner (1942) concluded from an analysis of the structural similarities of the two molecules and from McGimVy’s data (1942) that desoxycorticosterone is converted in the body to progesterone, probably by removal of the primary hydroxyl group. Since then, evidence has been presented for the in vivo conversion of DCA to progesterone in monkeys (Zarrow, Hisaw and Bryans, 1950) but no information is available regarding the locus of this conversion. MATERIAL AND METHODS Adult rats of the Sprague-Dawley strain and grey Chinchilla rabbits were used for the studies on the site of conversion of DCA to prog...

Seven goitrogens were studied to determine whether adrenal atrophy was a characteristic response to administration of antithyroidal agents. Treatments consisted of administration of thiouracil (0.1%), Tapazole (Lilly, 0.001%, 0.005% and 0.01%) and potassium perchlorate (1%) in drinking water and feeding of low iodine diet, p-aminosalicylic acid (PAS, 1%, 2%, 4%), p-aminobenzoic acid (PABA, 2%, 4%) and sulfaguanidine (2%, 4%) in the diet. After 12 weeks of treatment, the animals were anesthetized with sodium pentobarbital, blood was withdrawn by cardiac puncture for steroid analyses and the weights of the pituitary, thyroid, adrenal and thymus glands were determined. Treatment with thiouracil, Tapazole, perchlorate, PABA and sulfaguanidine induced an atrophy of the adrenal gland. Administration of PAS and the low iodine diet brought about hypertrophy of the thyroid gland without adrenal atrophy. Feeding with PABA, at the level of 2% in the diet, induced adrenal atrophy without thyroid hypertrophy while at the 4% level both thyroid hypertrophy and adrenal atrophy occurred. PABA at both dose levels brought about a shift in plasm corticoid levels. Plasmaa from rats given PABA was found to contain little or no corticosterone while the concentration of 17-hydroxycorticoids was markedly increased.

The isometric contractile response to oxytocin has been studied in vitro utilizing strips of tissue from rabbit mammary glands. Responses were maximal at resting tensions of 200–400 mg/mm2. The force of contraction increased from the beginning of lactation to about 9 days post partum and then leveled off. Little or no response is noted below 15° C and the maximum response is obtained in the range of 32 to36°C. Irreversible changes begin above 41° C. As little as 0.1 mU oxytocin/ml could be detected and the dose-response curve was demonstrated statistically to be linear between the dosages of 0.5 to 10 mU oxytocin/ml. The doseresponse curve reached a plateau at about 8–11 mU/ml. Replacing sodium with potassium resulted in a logarithmic decrease of contractile force with time. This decrease was partially reversible. The strip became inexcitable in calcium free Tyrode's solution. Excitability was again established by adding calcium. Other than to oxytocin, the mammary strip responded only to acetylcholine. The effect of acetylcholine could be blocked by atropine and this treatment did not affect the response to oxytocin. The site and mechanism of action of oxytocin are discussed.

SUMMARY The ovarian cholesterol depletion assay for luteinizing hormone (LH) was investigated in the untreated immature rat. The prepubertal rat is a satisfactory animal to use in this assay because the diurnal rhythm in ovarian cholesterol is not present until puberty. A dose-response curve was obtained between 2·5 and 10·0 μ LH and the average lambda was 0·17. The assay was specific for LH; the presence of other pituitary hormones had no significant effect on the relative potency of NIH-LH preparations. The assay is probably not sensitive enough for untreated plasma but had excellent reproducibility and is easily performed.