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Changes in small blood vessels of corpora lutea (CL) undergoing cyclical regression were studied by light and electron microscopy and the progesterone content of some CL was assayed. Vascular changes were 1st identified at Day 14 of the estrous cycle were consistently present by Day 16 and were observed in all CL in which progesterone content was less than 10 mcg/gm luteal tissue. Vascular changes involved both the luminal contents and walls of capillaries and small venules. Many capillaries contained degenerating cellular fragments incorporating nuclear and cytoplasmic remnants together with blood cells. The walls of many vessels containing cellular fragments appeared normal. In others abnormalities observed included folding of the basal lamina increase in the size and number of gaps in the endothelium increased endothelial cell projection into the lumen the inclusion of hetero- and/or autophagic vacuoles in the cytoplasm of many endothelial cells and pericytes and endothelial cell degeneration leading to ultimate disintegration of affected vessels. By Day 1 of the following cycle the number of capillaries was much reduced. It is concluded that at a relatively early stage of luteolysis many luteal capillaries show changes involving obstruction of the lumina by large amounts of cellular debris at least a part of which is of endothelial origin. The relationship of these changes to other phenomena associated with luteolysis is discussed.(Authors modified)

Synthetic gonadotropin releasing hormone (Gn–RH) which is identical to ovine LHreleasing hormone was given by intracarotid infusion (1.5 ng'hr for 4–5 hr) to ewesat various stages of their estrous cycle. It was found that LH and FSH responses to Gn–RH were significantly lower (p< 0.02) in the sheep infused on days 2–12 compared to sheep treated on days 15–17 after estrus. Continuous infusion of exogenous progesterone (500 'Mg'hr for 76 hr) significantly suppressed LH (p < 0.05) and FSH (p < 0.01) response to Gn–RH in ewes at the proestrous stage of their cycle. It is concluded that progesterone has a modulating influence upon LH and FSH secretion and could be responsible for thelower gonadotropin response to Gn-RH during the luteal stage of the cycle. (Endocrinology 95: 937,1974)

The total content of LH, FSH, and growth hormone was measured in pituitaries from anestrous ewes and from ewes at known stages of pregnancy. LH content was lower in the pregnant ewes than in the anestrous group. Compared with the anestrous group, a significant drop in mean LH content was seen by days 40-50 of pregnancy (894 vs 350 mug, P less than 0.001), and it reached its lowest value by 120-135 days of pregnancy (43 mug, P less than 0.001). In sheep 148 days of pregnant, mean LH content was higher than in the latter group (155 mug). The correlation coefficient between the stage of gestation and the LH content was 0.63 (P less than 0.01). There was no significant change in mean FSH content in ewes up to 135 days pregnant (range 1196-1550 mug) compared with anestrous ewes (1023 mug). In the group 148 days pregnant (531 mug), a significant decrease was seen compared with ewes at other stages of pregnancy (P less than 0.05). Stage of gestation and FSH content were poorly correlated (r = 0.07). No significant differences in growth hormone content were seen in any of the groups. The results suggest that the progressive reduction in LH response to synthetic GnRH which has been reported for pregnant sheep may be due to selective inhibition of LH biosynthesis.

SUMMARY The luteolytic properties of prostaglandin F2α (PGF2α) were studied in experiments on sheep with ovarian autotransplants. PGF2α was infused at the rate of 40, 10 and 2 μg/h for 4·0, 7·0 and 9·5–18·0 h respectively. At rates of 40 and 10 μg/h, progesterone secretion decreased to 50% of the control levels in 2·6 ± 1·4 h and fell to 8–30 μg/h within 36–52 h from the start of infusion. The onset of oestrus occurred 42–66 h after the infusions had started and a typical pre-ovulatory surge of luteinizing hormone (LH) was observed 52–66 h after infusing PGF2α. On occasions, this surge was accompanied by a brief peak of oestradiol-17β secretion and shortly thereafter ovarian steroidogenesis decreased to very low levels. In four sheep infused at a rate of 2 μg/h, peripheral progesterone values decreased gradually and only one animal returned to oestrus. It would seem that 2 μg/h is close to the minimum intra-arterial dose to cause luteolysis in the sheep.

Sheep grazing the oestrogenic varieties of subterranean clover ( Trifolium subterraneum L.) exhibit an irreversible loss in fertility that has been associated with changes in the mec

Part. I: Prostaglandin F2Α (PGF2Α) was shown to be ‘the’ luteolysin in the ewe on the following criteria: (1) Hysterectomy and/or separation of the uterine horn from the ovary bearing a corpus luteum led to prolongation of the oestrous cycle, (2) PGF2Α shortened the cycle when administered in the midluteal phase, (3) PGF2Α was identified in uterine venous blood, (4) a mechanism for the transfer of PGF2Α from the uterine vein to the ovarian artery was shown to exist, (5) the quantitative aspects of the secretion transfer mechanism and luteolytic potency of PGF2Α were adequate to account for the observed phenomena. Part II: These criteria were applied for evaluation of PGF2Α as ‘the’ luteolysin in the following species: cattle, goat, horse, pig, guinea pig, rat, hamster, rabbit, monkey, human. On present knowledge, there appeared to be a variation between species from those in which PGF2Α was probably concerned in luteolysis and those in which the evidence was against such a role. Part III: PGF2Α was shown to be luteolytic when given by continuous infusion for 3–6 h into the lumen of the uterus in cattle as well as sheep. The minimum effective dose was of the order of 7 g/kg. The application of this finding to artificial insemination programmes was discussed.

A heterologous radioimmunoassay system, using an antiserum to human FSH in combination with radioiodinated ovine FSH was highly specific for FSH for a number of species, and was used to measure plasma FSH levels in sheep, rat and man in a range of physiological states. Within-assay coefficient of variation (CV) was

STUDIES ON A RADIOIMMUNOASSAY FOR OVINE FOLLICLE STIMULATING HORMONE: INTERFERENCE BY OVINE ALBUMIN

Synthetic gonadotropin-releasing hormone (Gn-RH) was administered by intracarotid infusion (1.5 µg⁄hr for 5 hr) into groups of ewes at 6, 13 and 18 weeks gestation, at about the time of parturition and at 3 and 6 weeks postpa. rtum. There was a progressive decrease in the LH response to Gn-RH during gestation with no detectable LH release by 18 weeks. Little or no responsewas obtained at term or 3 weeks postpartum, and recovery was only partial as late as 6 weeks after delivery. (Endocrinology 94: 291, 1974)

The numbers of primordial follicles in ovaries of ewe lambs, from two groups of Peppin Merinos that had been selected for (T group) and against (0 group) mUltiple births, were estimated at birth, 7 days and 5 months of age. Peripheral plasma and anterior pituitary levels of LH and FSH were determined by radioimmunoassay in the lambs at 5 months of age. These lambs were either entire or unilaterally ovariectomized (hemispayed) at 7 days of age.

A synthetic decapeptide (Gn-RH) structurally identical to ‘ovine LH-releasing hormone’ was given by intra-carotid infusions (0, 0.5 and 1.5 µ g/h for 3 h) to two groups of ewes late

Serial measurements (up to four times per day) of maternal plasma progesterone, corticosteroids, estrone, estradiol-17�, LH, and prolactin have been made in six sheep, during late pregnancy and at parturition (Day 0). The mean progesterone concentration on Day -10 was 15.5 ng/ml. From Day -4 the level began to decrease and by Day 0, the mean progesterone level was 1.0 ng/ml. The mean concentrations of estrone and estradiol-17p on Day -3 (62.4 and 24.0 pg/ml, respectively) began to rise during the 48 hr preceding parturition, reaching peak values of 228.0 and 141.8 pglml, respectively. The mean corticosteroid level (17.3 ng/ml) rose during the 18 hr preceding parturition, reaching a peak of 38.6 ng/ml. Estrone, estradiol-17�, and corticosteroids returned to low levels within 12 hr after parturition. LH levels remained relatively coastant (2.0-6.0 ng/ml) from -36 h to +30 h but prolactin levels rose sharply from about Day -2. Possible explanations for the absence of an increase in LH secretion, in response to the preparturient rise in estrogens, are discussed.

The plasma FSH and LH responses to 17β–estradiol (E2) or to a synthetic gonadotrophin— releasing hormone (Gn—RH) were examined in anestrous ewes. FSH was measured by a heterologous double—antibody radioimmunoassay, while LH was estimated using a solid—phase method. Intravenous infusions of E2 (10 μg/hr for 4 hr) caused the plasma concentration of FSH to rise from 20–130 ng/ml NIH—FSH—S6 to peak values of 190, 350, and 400 ng/ml, respectively, in 3 animals. The release of FSH occurred over the same time interval as that previously reported for LH. In 2 animals, intracarotid infusions of Gn—RH (1.5 μg/hr for 3 hr) caused significant increases in both gonadotrophins which again rose and fell together. Plasma FSH concentrations rose from 38 and 70 ng/ml to a peak of 110 and 160 ng/ml after iy2 and 3 hr, respectively. These findings are consistent with the concept that Gn— RH is the mediator of the estrogen—induced release of LH and FSH which occurs at estrus. (Endocrinology 92: 862, 1973)

Ovarian weight has been shown to increase markedly in the newborn ewe lamb, and factors which might contribute to this growth were examined. Follicle development was studied in the ovaries of 28 lambs aged 0, 2, 4, 6, 8 and 10 weeks. Plasma samples, pituitaries and one ovary were assayed for gonadotrophin or steroid hormone content. No significant differences between age groups were found in pituitary LH concentration or mean plasma LH. Pituitary FSH concentration increased with age, except for a small decrease at 8 weeks, but no significant changes were seen in plasma FSH. Ovarian progesterone and oestradiol concentrations did not appear to be associated with follicular development. Growing follicles were most numerous at 2 weeks whilst total vesicular follicles reached a peak at 4 weeks. Most vesicular follicles were less than 1.4 mm in diameter. Advanced atresia in vesicular follicles became apparent by 4 weeks although early signs were present in younger lambs. Fluctuations in gonadotrophin levels do not appear to be responsible for variations in number and size of vesicular and growing follicles in the lamb ovary. Other possible explanations are discussed.