The studies described in this thesis were designed to investigate the control of inhibin production, secretion and localization in the primate ovary. A heterologous radioimmunoassay was established and validated for the measurement of inhibin during the normal menstrual cycle in the stumptailed macaque (Macaca arctoides) and ovulatory cycle in the common marmoset monkey (Callithrix jacchus). The pattern of immunoreactive inhibin secretion was low during the follicular phase, reaching maximum levels during the mid -luteal phase in both species. This is similar to the pattern observed in the human. These results suggest that the corpus luteum is a major source of immunoreactive inhibin secretion in the primate. Inhibin concentrations remained elevated in pregnant marmosets throughout gestation.
The gonadotrophic control of inhibin production was investigated in vivo by administration of a luteinizing hormone releasing - hormone (LHRH) antagonist in the stumptailed macaque during the mid -luteal phase. Treatment with LHRH antagonist for 3 days resulted in permanent suppression of luteal function as shown by low serum concentrations of progesterone and immunoreactive inhibin. Replacement of gonadotrophin with human chorionic gonadotrophin (hCG) but not follicle - stimulating hormone (FSH) prevented gonadotrophin induced suppression by antagonist suggesting that inhibin, similar to progesterone, is integrated with the luteinizing hormone (LH) control of the corpus luteum. The control of inhibin secretion was further investigated in an in vitro luteal cell culture system. Human luteal cells secreted progesterone, oestradiol and inhibin in culture. Inhibin secretion by the luteal cells was stimulated by hCG in a dose -dependent manner providing further evidence that the secretion of inhibin is under the control of LH.
In an attempt to obtain a model of transitory suppression of luteal function, the effect of treatment with LHRH antagonist for 1 or 2 days during the mid -luteal phase on serum concentrations of progesterone and inhibin was compared. Recovery of progesterone and inhibin secretion was observed in two out of six macaques treated with two injections of antagonist and in three out of six treated with a single injection of antagonist. Therefore, with the regimens of LHRH antagonist employed, this approach was not conducive to obtaining a reliable transitory suppression of luteal function. The effect of ovarian hyperstimulation with FSH on serum concentrations of immunoreactive inhibin in stumptailed macaques in which endogenous gonadotrophin secretion and ovarian activity had been suppressed by an LHRH agonist implant was
viii studied. LHRH agonist treatment suppressed both steroids and inhibin. Administration of FSH for 9 days, 8 weeks after agonist implant, resulted in marked elevations in oestradiol and immunoreactive inhibin. This nonphysiological situation demonstrated that developing follicles may be a source of inhibin. However it requires the growth of multiple antral follicles to induce a marked rise in immunoreactive inhibin during follicular development.
Inhibin was localized immunocytochemically in the primate ovary using an avidin- biotin immunoperoxidase technique. Intense immunostaining for inhibin a- and I3- subunits was detected within the granulosa- lutein cells of the human corpus luteum. Similar distribution of inhibin a- subunit immunostaining was observed in 12 corpora lutea obtained during early -, mid- and late -luteal phases of the menstrual cycle and no changes in intensity or distribution of staining were apparent at these different stages. The specific localization of inhibin within the granulosa- lutein cells suggests that inhibin production may originate from a discrete cell population within the corpus luteum.