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The removal of the thyroid gland in newborn or in young adult rats causes reduction in the number of peripheral blood lymphocytes and depression of either the humoral immune reactions against sheep and chicken red blood cells or the response of spleen cells to phytohaemagglutinin. These immunological defects are fully established in perinatally thyroidectomized rats after weaning, while in animals thyroidectomized in young-adult age they are observable 45-60 days after the operation. In both cases daily injections with thyroxine can completely restore the lymphoid system of thyroid-deprived animals. These results stress the importance of thyroid hormones for lymphocyte proliferation either during the period of ontogenetic development or in adult life [ABSTRACT FROM AUTHOR]

The control of adenylate cyclase activity by lipolylic hormones was studied in fat cell "ghosts" in the presence and absence of physiological concentrations of insulin. Insulin was found to inhibit the effect of submaximal concentrations of norepinephrine, adrenocorticotrophin, and glucagon. Addition of the hormone to the assay system leads to an immediate reduction of the linear rate of formation of adenosine 3′:5′-monophosphate (3′:5′-AMP). For norepinephrine and adrenocorticotrophin a dose-response relationship was established which was shifted by insulin in a "pseudocompetitive" fashion. Increasing the concentration of insulin beyond the physiological range resulted in a reversal of its inhibitory effect in the presence of lipolytic hormones. Insulin alone at concentrations between 5 and 5000 µU/ml had no effect, whereas a small stimulatory effect of high insulin concentrations (5 - 500 mU/ml) could be found in the presence of submaximal concentrations of norepinephrine. No effect of insulin was obtained against several concentrations of NaF. The effect of insulin upon the norepinephrine-stimulated adenylate cyclase disappeared after trypsin treatment of intact cells prior to preparation of ghosts. Further incubation of intact fat cells after trypsin treatment lead to a recovery of the effect of insulin. Analogous to insulin, nonsuppressible insulin-like material which is believed to be related to "somatomedin", was found to inhibit adenylate cyclase activity in ghosts, but this effect was not abolished by trypsin treatment. Ghosts were found to contain 3′: 5′ -- AMP phosphodiesterase activity which was not influenced by direct addition of insulin as measured with low substrate concentrations or under the conditions of the adenylate cyclase reaction. It is suggested that insulin at low concentrations interferes with the activation of the adenylate cyclase system by lipolytic hormones, at a step between hormone receptor and catalytic unit. In view of similar characteristics of the antilipolytic effect of insulin in intact lipocytes and the observed modulation of the action of lipolytic hormones in ghosts, a fundamental physiological role of this effect upon the adenylate cyclase system in the mechanism of action of insulin is postulated. [ABSTRACT FROM AUTHOR]

The activities of adenyl cyclase, the phophodiesterases of low and high Km and the tissue content of adenosine 3':5'-monophosphate (3':5'-AMP) in the mammary glands of rats at different stages of the lactation cycle have been measured. The effect of in vitro F¯, Ca2+ and of the hormones progesterone, β-estradiol, hydrocortisone, insulin and prolactin on the adenyl cyclase activity of membrane fractions isolated from the mammary gland of pregnant and lactating rats has been investigated. The results show that there is a coordinated change of the activities of the enzyme adenyl cyclase and 3':5'-AMP phosphodiesterase and the tissue content of 3':5'-AMP at different stages of the lactation cycle with the activity of adenyl cyclase and the cyclic nucleotide rising to a peak at the end of pregnancy and then falling sharply after parturition. The reverse pattern was observed for the 3':5'-AMP phosphodiesterase activity. F¯ (1 - 10 mM) consistently produced an inhibition (40%) of adenyl cyclase activity of mammary glands from pregnant rats while having no effect on the enzyme from the lactating gland. Low concentrations of Ca2+ (1μM) activated the enzyme from pregnant glands and from those of early lactation by about 40% but had little effect on the glands taken from rats of mid-lactation. Increasing the Ca2+ concentration led to a decline of this effect and eventual inhibition at 5 mM, the effect being most marked on the fully lactating gland. Progesterone and β-estradiol consistently caused a considerable stimulation (80 and 50% respectively) of the adenyl cyclase activity of the pregnant gland; hydrocortisone, insulin and prolactin did not. None of the hormones tested activated the adenyl cyclase activity of the lactating gland and insulin appeared to inhibit it severely. The results, which suggest that the growth and development of the mammary gland is related the tissue content of 3':5-AMP while the initiation and scale of lactation may be related to ties removal, are discussed in relation to development, lactogenesis and milk ejection and the complex endocrine control of these processes. [ABSTRACT FROM AUTHOR]

The properties of porcine thyroid-stimulating hormone and its subunits, which had not yet been fully characterized, are presented A new procedure is described for the isolation of the hormone using only ion-exchange chromatography and gel filtration The system, presented in details for porcine thyrotropin was also applied with success for the preparation of bovine and human thyrotropins. The porcine hormone prepared either by the new chromatographic procedure or by countercurrent distribution exhibited identical physicochemical and biological characteristics. The subunits α and β of porcine thyroid-stimulating hormone were also obtained by a new procedure. In this method, the native hormone was incubated in acidic urea and the chains were than separated by ion-exchange chromatography. The subunits were submitted to a complete characterization. The amino-acid composition of the α subunit of porcine thyrotropin was found identical to that of α chain of porcine luteinizing hormone. Its amino-terminal sequence was NH2-Thr-Met-Glx indicating that the ,:α-chain of porcine thyrotropin is shorter by six amino acids than its bovine counterpart. The porcine β subunit differs markedly in its amino-acid composition from the bovine β chain particularly with respect to lysine, histidine, tyrosine, threonine and Nutamic acid. Phenylalanine is the amino-terminal residue of the polypeptide chain. The carbohydrate compositions of the two subunits are presented. Porcine thyrotropin differs from its bovine counterpart in that it contains sialic acid, present only in the α subunit. [ABSTRACT FROM AUTHOR]

The iodination of porcine luteinizing hormone and its subunits, in the presence of lactoperoxidase and hydrogen peroxide has been studied as a function of iodide concentration. The maximum incorporations were 11 iodine atoms per molecule of hormone while it was possible to incorporate up to 10 and 5 iodine atoms per molecule in the isolated α and Β subunits respectively. Both tyrosyl residues of the Β subunit (Β-37 and Β-59), readily iodinated when the subunit, is isolated, are found to be non-reactive in the native hormone. They could thus bc located on poly peptide portions involved in the binding of the subunits. The reactivities of the tyrosines of porcine luteinizing hormone were found to be in the order: α-21 > α-92 ... α93 > α-41 > α-30 ... Β-37 ... Β-59. The susceptibility of peptidic bonds α-20α-21 and α-24-α-25 to trypsin indicates that this part of the molecule, containing Tyr-α-21, is at the surface of the hormone in aqueous solution. Although the Lys-α-95-Ser-α-96 bond is susceptible to trypsin it is not cleaved by carboxypeptidases. Thus, the carboxy-terminal part of the α chain in the native hormone is at the surface of the molecule but its carboxyl end is probably shielded. [ABSTRACT FROM AUTHOR]

The specific activity of the enzyme tyrosine 2-oxoglutarate transaminase from an established rat liver-cell line grown in chemically defined medium, increases under the addition of the synthetic glucocorticoid dexamethasone sodium phosphate. Insulin also induces an enzyme increase but only in cells exposed previously to dexamethasone. Lower and ineffective glucocorticoid concentrations are, however, effective per se in making the cells insulin-sensitive. Optimal concentrations of the glucocorticoid increase the enzyme activity 3 to 4-fold during the first 8–9 h of incubation, however the cells are not insulin-sensitive until the tenth hour of incubation. These findings suggest that dexamethasone induces a factor(s) necessary for the insulin effects only on the enzyme since insulin increased the rate of labeled amino-acids incorporation in trichloroacetic acid precipitates without need for cell pretreatment with the other hormone. Dexamethasone was found to increase the rate of labeled uridine incorporation into trichloroacetic acid precipitates. Experiments using RNA and protein-synthesis inhibiters indicate that dexamethasone operates at a transcriptional level, while insulin works at a translational level. Actinomycin does not ‘superinduce’ the enzyme, however when the cells are preincubated with medium plus serum the above mentioned phenomenon reappears. At least two forms (I and II} of the enzyme have been observed ill the cells by hydroxyapatite column chromatography using a phosphate step gradient. Both forms are inducible by dexamethasone. Form I is extremely heat-senzitive (65°C) while form II is completely heat-resistant in the same condition. Incubation of the cells with dexamethasone does not change the heat stability of form II but increases significantly the resistance of form I to heat treatment. Insulin appears not to affect the heat stability of the enzyme. [ABSTRACT FROM AUTHOR]

1. The properties of protein kinase in extracts of rat diaphragm has been studied. Investigations on protein kinase has also been made after preincubation of the diaphragms with epinephrine or insulin. Protein kinase activity was measured by the rate of incorporation of 32P from [γ-32P]ATP into histone in the absence and the presence of cyclic AMP. In addition the binding of cyclic [3H]AMP by the extracts was investigated. Furthermore, the cyclic-AMP-dependent and -independent enzymes were separated by gel filtration on Sephadex G.150. 2. Protein kinase activity in crude extracts was increased 2- to 3-fold by cyclic AMP. The cyclic-AMP-dependent activity was relatively stable during purification with ammonium sulphate and recovered to an extent of 70%. The cyclic-AMP-dependent activity in crude extracts was recovered as a separate peak by gel filtration on Sepbadex G-150. Purified cyclic-AMP- dependent protein kinase was quantitatively recovered when added to a crude muscle extract. It is indicated that the cyclic-AMP-dependent protein kinase in muscle extracts quantitatively reflects the amount of the inactive holoenzyme in the tissue. 3. Protein kinase activity independent of cyclic AMP was inactivated by crude muscle extracts. This was demonstrated by preincubation of muscle extracts with cyclic AMP. Dissociation of the holoenzyme by cyclic AMP as demonstrated by a decrease of cyclic-AMP-dependent activity and a decreased binding of cyclic [3H]AMP was not accompanied by a change in the cyclic-AMP-independent activity. Purified cyclic-AMP-independent protein kinase added to crude muscle extracts was also inactivated. A small peak of cyclic-AMP-independent activity was obtained when crude extracts were subjected to gel filtration on Sephadex G-150. This peak was increased 2- to 3-fold when elution was done in the presence of 0.5 M NaCl. It is indicated that the active catalytic subunit of protein kinase in the tissue mainly is converted to an inactive complex in muscle extracts. 4. After preincnbation of rat diaphragms with epinephrine the cyclic-AMP-dependent activity as well as the binding of cyclic [3H]AMP were decreased. This was demonstrated both in crude muscle extracts and in purified enzyme preparations of protein kinase from the extracts. 5. After preincubation of rat diaphragms with insulin the opposite effects could be demonstrated. Both in crude extracts and purified enzyme preparations the binding of cyclic [3H]AMP and the cyclic-AMP-dependent protein kinase activity were increased. 6. By gel filtration of rat diaphragm extracts on Sephadex G-150 it was demonstrated that preincubation of the diaphragms with epinephrine resulted in decreased cyclic-AMP-dependent protein kinase, whilst the cyclic-AMP-independent enzyme was increased. The opposite effects were seen by preincubation of the diaphragms with insulin, i.e. increased cyclic-AMP-dependent and decreased cyclic-AMP-independent enzymes. 7. It is indicated that important metabolic effects by epinephrine and insulin are mediated by modulation of the activity of protein kinase in the tissue. The effect by epinephrine on protein kinase is attributed to the increase of cyclic AMP concentration. The mechanism of the action of insulin on this enzyme is discussed. [ABSTRACT FROM AUTHOR]

The venom of Dendroaspis viridis has been fractionated by chromatography on Sephadex G-50 and SE-Sephadex. Thirteen polypeptides containing either 59–63 amino acid residues and four disulphide bridges or 71–73 amino acid residues and five disulphide bridges have been isulated and characterized by amino-acid analysis and N-terminal residue determination. The compositions of the polypeptides show many similarities but the toxicities vary in excess of 100-fold, upwards from an LD50 of 0.08 mg/kg in mice. Enzymic and nerve growtJa factor activities have been located in protein fractions associated with higher molecular-weight material. [ABSTRACT FROM AUTHOR]

Twenty adult male golden hamsters were isolated into individual cages for a period of six weeks, at the end of which time they had introduced into their home cages, on three occasions, a castrated male intruder. On each occasion the castrated intruder was daubed on the anogenital region with urine from one of three sources: (1) intact females, (2) other castrated males, and (3) intact males. Urine from a different source was applied to the castrated intruder on each of the three tests. Resident males consistently showed more aggression, sniffing, and following and less defensive behavior than the intruders. However, aggression by the resident males showed a significant variance over the three urine treatments given to the intruder. It is concluded that like male mouse urine, male hamster urine contains attack-provoking cues, but that unlike that of the mouse, female urine does not appear to be attack-inhibiting in this species. [ABSTRACT FROM AUTHOR]

Animal experiments in which the opportunity to aggress was positively reinforcing are surveyed, with attention paid to field and laboratory reports on play and play fighting. A distinction is drawn between ways in which aggressive behavior may be elicited and factors which increase or decrease the probability that aggression will be emitted. Since aggression may be emitted and may also be reinforcing, the possibility that aggressive behavior may be self-reinforcing is mentioned. In addition to positive reinforcement. consequences of aggressive behavior are presented. These include punishment, removal of a noxious stimulus, feeding, arousal, and disinhibition. [ABSTRACT FROM AUTHOR]

Among the many factors that control mammary gland growth, hormones play a leading role. To assess the importance of each factor on the growth of the gland, different methods have been devised. These methods are complementary hence no method is capable by itself of a total estimate of mammary growth. Fetal growth of the mammary rudiment is influenced by hormonal factors and at the same time (more than at any other stage of mammary growth) by the mesenchyme. A marked characteristic of the fetal period is the establishment of sexual dimorphism. This peculiar phenomenon has been studied in vitro. After birth, the gland falls under the direct control of stimuli from the hypothalamus pituitary axis. By means of its cyclic variations or changes conditioned by conception, growth is induced by pituitary hormones proper (prolactin growth hormone) or via the ovary or the adrenals. Other factors such as diet, age, mesenchyme, and genetic background modulate the action of hormones on the gland. The action of all these factors is examined in this paper throughout the life of different mammals, from the prepuberal stage, through adult nulliparous life, gestation, the maximal growth induced by the hormonal levels of lactation, and in regression (produced alter hormone removal). In vivo and in vitro studies have been correlated in demonstrate which of the stimuli induce mammary cell replication and growth in the preneoplastic and neoplastic mammary gland. [ABSTRACT FROM AUTHOR]

The prepubertal mammary gland consists of simple ducts or tubes whose walls are composed of epithelial cells. The process of differentiation seems to include cellular proliferation at irregular sites along the wall of these ducts. The proliferating regions ultimately give rise to the alveoli, the site of milk secretion. Which hormone or hormones serve as the primary mitogenic agent or agents is not certain. However, under in vivo conditions, prolactin seems to be an especially potent mitogenic substance. Under in vitro conditions, insulin stimulates cell division for a time. During the proliferative phase, an increase in DNA indicates increased activity of the replicative process. Increased RNA synthesis also indicates an enhancement of the transcriptional process. Cortisol stimulates synthesis of the rough endoplasmic reticulum and ribosomes and stabilizes the rough endoplasmic reticulum-ribosome complex. There is evidence that prolactin also stimulates secretory protein formation. Several hormones are involved in the complete differentiation process of the secretory epithelial cell. It is not clear whether a given hormone acts as a single focus or at several foci. There is evidence that several hormones do affect equivalent events in the differentiation process. [ABSTRACT FROM AUTHOR]

The discovery of specific effects produced on a given tissue by a biochemical molecule provides a potentially important base for further studies. Thus the finding that some hormones produce various effects on sebaceous glands adds another dimension to the growing store of information about these glands. Among the hormones from the anterior pituitary, thyroid, adrenal cortex, and gonads reported to affect the structure and function of sebaceous glands, androgens clearly are the most potent. In most species, many glands, especially those of the general body skin, are androgen sensitive and increase in size, and the individual cells become larger.

It is clear from the foregoing considerations that the development and secretory activity of the sebaceous gland of man is influenced by hormonal factors. Androgenic steroids, particularly of gonadal origin, are the hormones principally responsible for these effects and the only ones shown to have a direct stimulatory effect on glandular activity. Adrenal androgens may be responsible for early sebaceous gland maturation in late childhood, at a time when minor degrees of acne sometimes occur. Glucocorticoids appear to function in a permissive capacity, the anterior pituitary hormones primarily affecting the sebaceous gland indirectly through stimulation of their respective target organs, i.e., the gonads and the adrenal gland. The role of the thyroid and other endocrine glands is unknown and needs to be studied. [ABSTRACT FROM AUTHOR]

There are numerous ways of assessing the activity of the sebaceous glands in rodents. For example, gland size and the incidence of mitoses have been extensively used. Gland size is extremely tedious to measure and, since it depends on both the transit time of the sebaceous cells and their production, is not proportional to sebaceous output. Whereas the incidence of mitoses is a true measure of activity in a holocrine structure, it is only one factor in secretion, which also depends on intracellular synthesis. For these reasons, direct measurement of sebaceous secretion is desirable.

The effect of two anabolic hormones on wound healing was studied. Following the extraction of a lower first molar, ten normal hamsters received intraperitoneal injections of Durabolin, ten received Synthroid, and ten were given Durabolin and Synthroid. Ten controls received saline injections. Two animals from each group were sacrificed at 4, 8, 12, 16, and 20 days post extraction. Histological sections revealed the following changes: Animals treated with Durabolin exhibited fewer inflammatory cells, significant earlier bone fill and more accelerated reepithelization than the controls. The group receiving Synthroid produced bone replacement earlier than the controls. Epithelization occurred at essentially the same rate. When Durabolin and Synthroid were administered simultaneously, the animals demonstrated fewer inflammatory cells and less bone fill than the controls. [ABSTRACT FROM AUTHOR]

Crude human skin extracts having tissue-specific mitotic inhibitory activity (chalone), were studied by ethanol precipitation and disc gel electrophoresis. Precipitates obtained at various ethanol concentrations were dialyzed, lyophilized and tested for their mitotic inhibitory activity. It was found that the greatest inhibitory activity was concentrated in the precipitate formed in 81% ethanol, the active principle being concentrated about 200 times. Proteins in crude extracts were separated by disc gel electrophoresis, and at least eight bands were identified. Groups of bands were extracted from the electrophoretic gels and tested for their mitotic inhibitory activity. Fraction II, containing two bands, had the highest activity. Disc gel electrophoretic analysis of the 81% ethane precipitate revealed only two major bands, one of which could also be found in fraction 11 of the crude extract. This protein band, which is present in both of the mitotic inhibitory samples, may represent the human epidermal chalone. [ABSTRACT FROM AUTHOR]

This article presents information about acne. A great many adolescents suffer from acne most commonly on the face and between the shoulders, and occasionally elsewhere. The sebaceous glands become large and filled with secretions. Superimposed infection with skin bacteria leads to the formation of inflamed papules, pustules, and reddened scars. The tendency to acne typically begins between age 10 and 14, being related to pubescence, and fades away when adulthood is reached. Clearly, the sebaceous glands in the susceptible areas are stimulated by the pubertal androgenic hormones which enter the circulation from the gonads and the adrenal cortex. There is no known way of arresting the basic tendency to acne. Much can be done, nevertheless, to suppress the number and prominence of the lesions. Blackheads can be evacuated with an extractor, a metal strip whose rounded end has a hole in the middle which can be pressed down around the blackhead with a slight sliding movement. These extractors can be bought at neighborhood drug stores.

5′-Guanylylimidodiphosphate (GMP-PNP) had a biphasic effect on basal adenylate cyclase activity of rat fat cell ghosts, being inhibitory and stimulatory while GTP was mainly inhibitory. At low concentrations of GMP-PNP a transient inhibitory phase preceded the onset of activation. This initial inhibition was overcome by higher concentrations of GMP-PNP, ATP or magnesium. The stimulatory effects of GMP-PNP were increased by high concentrations of ATP or magnesium, the apparent K for activation being a function of time. After 5 min of incubation half-maximal activation was obtained at 3 μM GMP-PNP, after 20 min of incubation the K for GMP-PNP was found to be between 0.1 and 0.3 μM. After 20 min of incubation a 15fold increase of cyclase activity above basal level was observed in the presence of 1 μM GMP-PNP. GTP competitively inhibited the stimulant effect of GMP-PNP. On the other hand, it activated basal activity only under carefully selected conditions. GMP-PNP and noradrenaline had a synergistic action on cyclase activity. At high substrate concentrations (1 mM ATP) GMP-PNP shifted the apparent K for activation by noradrenaline from 3 μM to 0.1 μM. At low substrate and high magnesium concentrations 1 μM noradrenaline was unable to stimulate adenylate cyclase. Under these conditions GMP-PNP facilitated the stimulation by the hormone, although GMP-PNP itself inhibited basal activity. It is suggested that GMP-PNP activates the adenylate cyclase by competing at a common nucleotide binding site with inhibitory agents such as free ATP or GTP. Moreover, the guanyl nucleotide analogue may initiate conformational changes of the enzyme system which facilitate the response to hormones. [ABSTRACT FROM AUTHOR]

Contradictory results on the role of NaK-ATPase as the diuretic receptor are reported in the literature. In own experiments the effects of 1 mM ouabain and 0.2 mM ethacrynic acid on fractional sodium reabsorption and oxygen consumption was investigated in an isolated perfused kidney system. NaK-ATPase was measured in basal-lateral membranes of kidney cortex tubular cells. Combination of ouabain and ethacrynic acid resulted in a complete inhibition of fractional sodium reabsorption at only a 46% inhibition of NaK-ATPase activity. The complete inhibition of sodium reabsorption at only a partial inhibition of NaK-ATPase probably is caused by additional metabolic effects of ethacrynic acid. It is suggested that NaK-ATPase is not the only diuretic receptor. - Another enzyme possibly involved in the control of sodium transport and water permeability is the renal adenyl cyclase. 1 mM furosemide and 1 mM ethacrynic acid inhibited the enzyme in homogenates of the kidney cortex and inner medulla, while amiloride was without any effect. In the cortex the furosemide induced inhibition of adenyl cyclase can be reversed by 1 U parathyroid hormone and 0.1 mM isoproterenol. The ethacrynic acid effect on adenyl cyclase was not influenced by isoproterenol. In the inner medulla 1 mU antidiuretic hormone but not isoproterenol antagonized the furosemide inhibition of adenyl cyclase. Antidiuretic hormone and isoproterenol exerted no effect on the ethacrynic acid inhibition of adenyl cyclase. It is suggested that furosemide and ethacrynic acid act at different sites of the adenyl cyclase or at a mixture of adenyl cyclases with different sensitivities. [ABSTRACT FROM AUTHOR]

The age at which female mice attain puberty depends to a large extent on their prior experience with male stimuli. Females exposed to male odors mature more rapidly than those denied access to the smell of a male. Such an odor can be termed a priming pheromone because it sets in motion a chain of physiological events which, in this case, culminate in puberty. The demonstration that a social factor such as a pheromone can influence the rate of sexual development in the mouse may have implications for man. It seems likely that a complex of stimuli, certainly not odors alone, may have contributed to the accelerated rate of human sexual maturation which has occurred during the past century. [ABSTRACT FROM AUTHOR]