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Summary.The implantation of Silastic capsules containing androstenedione (release rate 63·2 ± 4·4 μg/24 h) into 4-day cyclic rats resulted in a prolongation of the cycle (P< 0·001), most rats showing 5-day cycles after the first, largely unaffected cycle. There was a reduction in ovulation rate (P< 0·01) and lower serum LH levels on the morning of oestrus (P< 0·01) but serum FSH levels were unaffected.

Androstenedione and oestradiol were measured by radioimmunoassay in the utero-ovarian venous plasma of two ewes during anoestrus. The concentrations of both steroids were significantly higher than the corresponding concentrations in peripheral plasma, indicating that androstenedione and oestradiol are secreted by the ovary during anoestrus.The concentration of LH during anoestrus was measured by radioimmunoassay in jugular venous plasma of control ewes, ewes immunized against 11α-OH-androstenedione–bovine serum albumin and ewes that had been ovariectomized and hysterectomized 9 months previously. During a 12 h sampling period, discharges of LH occurred more frequently in the immunized ewes than in the control group but less frequently than in the ovariectomized group. The frequency of discharge was positively correlated with the titre of androstenedione antibodies in the immunized animals.After injection of 25 μg oestradiol benzoate (OB) all controls, 3 out of 5 immunized and 4 out of 5 ovariectomized–hysterectomized ewes showed positive feedback. No positive feedback occurred in the two ewes with the highest antibody titres to androstenedione, but negative feedback in response to OB appeared to function normally in all the androstenedione immunized sheep. It is postulated that androstenedione, or one of its metabolites, normally modulates the effects of oestradiol in the control of gonadotrophin secretion in the ewe.

The concentrations of LH and FSH in jugular venous plasma were measured during anoestrus in control ewes and ewes actively immunized against 17β-oestradiol-6-(O-carboxymethyl)oxime–bovine serum albumin, oestrone-6-(O-carboxymethyl)oxime–bovine serum albumin or testosterone-3-(O-carboxymethyl)oxime–bovine serum albumin. During a 12 h sampling period, the basal level of LH and the frequency of LH pulses were significantly increased in all the immunized animals. The plasma FSH concentration was increased in two out of five oestradiol-immunized ewes and two out of three oestrone-immunized animals. The plasma FSH concentration in the testosterone-immunized animals was similar to the control values.Significant titres of antibodies to oestradiol-17β were found in all the immunized animals. It is suggested that binding of oestradiol-17β in the circulation by antibodies reduced the negative feedback action normally exerted by this steroid on LH secretion and, to a lesser extent, on FSH secretion. However, since the oestradiol antibody titres in the testosterone-immunized and oestrone-immunized ewes were considerably lower than those found in the oestradiol-immunized animals, it is possible that testosterone and oestrone, perhaps by acting as prehormones, could influence the negative feedback control by oestradiol-17β of gonadotrophin secretion in the anoestrous ewe.

Peritoneal fluid was aspirated during laparoscopy from normal women at various stages of the menstrual cycle. The volume of the fluid was found to be influenced by the stage of the cycle, rising from an early proliferative mean value of 0·8 ml to a mean volume of 18·7 ml after ovulation and decreasing again to a mean volume of 5·4 ml in the late secretory phase. The mean volume of peritoneal fluid obtained from women using the contraceptive pill was 0·8 ml, whereas only negligible amounts of fluid were aspirated at laparotomy from the peritoneal cavity of men.Despite marked changes in volume, the total protein content of the peritoneal fluid (± 60% of the concentration measured in plasma) remained fairly constant throughout the cycle, although a slightly, but significantly, lower value was found in the late proliferative phase. After ovulation the concentration of oestradiol and progesterone in the peritoneal fluid was higher than in plasma in the majority of cases, suggesting that some follicular fluid had drained into the peritoneal cavity at that time. Progesterone, in contrast to oestradiol, was also found in higher concentrations in peritoneal fluid than in plasma before ovulation.These results suggest that the volume and ovarian steroid concentration of peritoneal fluid are influenced by cyclic ovarian activity. At least two mechanisms may account for these observations: changes possibly effected by oestradiol in vascular permeability leading to a change of inflow and outflow equilibrium at the level of the peritoneal membranes and ovarian–peritoneal transfer of fluid after and possibly also before follicular rupture.

Summary.The concentrations of prostaglandins F-2α, E, D-2 and 13,14-dihydro-15keto PGE were measured in follicular fluid collected from women undergoing routine laparoscopy following induction of follicular development with clomiphene and hCG. Laparoscopy was performed before, or at 12, 24 or 36 h after administration of hCG. Prostaglandins were measured as the methyloxime derivative by radioimmunoassay. Peaks in PGE and PGF-2α concentration occurred at 12 and 36 h with a significant nadir at 24 h, whereas PGD-2 production was very low at 36 h. The concentration of PGF-2α rose significantly between 0 and 36 h and was greatest in follicles yielding oocytes, suggesting a possible role for this prostaglandin in the mechanism of follicle rupture.

Summary.The secretion rates of testosterone measured during the last half of the oestrous cycle in 2 Merino crossbred ewes with utero-ovarian autotransplants were 1·95 ± 0·34 ng/min and 2-48 0-63 ng/min. The secretion rate of testosterone was not correlated with the secretion rate of oestradiol or androstenedione in either ewe.Welsh Mountain ewes were actively immunized against testosterone-3-(0carboxymethyl)-oxime-bovine serum albumin (testosterone-3-BSA) or BSA alone (controls). Immunization against testosterone-3-BSA (5 ewes) resulted in anovulation (2 ewes) and the disruption of oestrous cycles and irregular ovulations (2 ewes). The ovaries showed morphological and endocrinological evidence of over-stimulation. Numerous large non-atretic follicles were present and in those ewes still ovulating the numbers of corpora lutea (ovulation rate) were increased. The concentrations of androstenedione and of oestradiol in the ovarian venous plasma were also markedly increased when compared to those in control ewes. The plasma binding capacity for steroids and the jugular venous concentrations of steroids were higher in immunized ewes. The binding capacity of follicular fluid for testosterone was similar to that of jugular venous plasma from the same ewe.These results show that immunization against testosterone-3-BSA leads to a disruption of ovarian cycles and ovarian over-stimulation.

Summary.Ewes were actively immunized against oestrone-6-(O-carboxymethyl)-oxime–bovine serum albumin, 17β-oestradiol-6-(O-carboxymethyl)oxime–bovine serum albumin or bovine serum albumin (controls). All 4 control ewes, 1 of 5 oestradiol-immunized ewes and 1 of 5 oestrone-immunized ewes had regular oestrous cycles. The other animals displayed oestrus irregularly or remained anoestrous. The plasma concentrations of LH and, to a lesser degree, FSH were increased relative to those in control ewes on Days 11–12 after oestrus or a similar total period after progestagen treatment in ewes not showing oestrus.The ovaries were examined and jugular venous blood, ovarian venous blood and follicular fluid were collected at laparotomy on Days 9–10 of the oestrous cycle. The ovaries of immunized ewes were heavier than those of control ewes. There were no CL in 5 of the immunized ewes but in the other 5 there were more CL than in the control ewes. Ovaries from 4 of 5 oestrone-immunized ewes contained luteinized follicles, while ovaries from 4 of 5 oestradiol-immunized ewes contained very large follicles with a degenerated granulosa and a hyperplastic theca interna. Both types of follicles produced progesterone, detectable in ovarian venous plasma and production of other steroids, particularly androstenedione, was also increased. The steroid-binding capacity of plasma was increased in the immunized ewes. The binding capacity of follicular fluid for oestradiol-17β and oestrone was similar to that of jugular venous plasma from the same ewes.These results suggest that immunization against oestrogens disrupts reproductive function by interfering with the feedback mechanisms controlling gonadotrophin secretion.

Summary.Ewes were immunized against androstenedione-11α-hemisuccinyl—bovine serum albumin (androstenedione-11–BSA) or BSA alone (controls). The ovaries were examined macroscopically and ovarian venous blood was collected at laparotomy by in-situ cannulation of the ovarian vein on Day 10 of the oestrous cycle, or by needle puncture of the ovarian vein 36 h after prostaglandin treatment. Follicular fluid was also collected from follicles >5 mm diameter in some ewes. Ovaries and adrenal glands were collected and examined histologically. Oestrone, oestradiol-17β, androstenedione, testosterone and progesterone were measured by radioimmunoassays. Immunization against androstenedione-11–BSA was followed by an increase in the number of surface follicles >3 mm in diameter and in ovulation rate. These changes were accompanied by an increased production of androgens (especially androstenedione) and of oestrogens during the preovulatory period. There were no observed changes in the adrenal cortex or pituitary glands, but the ovaries were heavier in immunized ewes and luteinized follicles were present in the ovaries of 1 of 4 immunized ewes.These results show that immunization against androstenedione-11–BSA leads to increased ovulation rate and suggest two possible mechanisms: (1) interference with the negative feedback effects of oestradiol-17β and/or (2) a reduction in the incidence of follicular atresia.