Dynamics of circulating concentrations of gonadotropins and ovarian hormones throughout the menstrual cycle in the bonnet monkey: role of inhibin A in the regulation of follicle‐stimulating hormone secretion

Abstract

In higher primates, increased circulating follicle-stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P(4)) secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern of P(4) secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3+/-2 vs. 27.3+/-3 pg/mL), and a 2- to 3-fold rise in circulating FSH levels by 24 hr (0.20+/-0.02 vs. 0.53+/-0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 microg/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P(4) concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase.

New targets for old hormones: inhibins clinical role revisited [Review]

“…Studies demonstrating the ability of human chorionic gonadotropin (hCG) to prevent the luteal regression and premenstrual decline of serum inhibin levels during the late luteal phase and following GnRH antagonist administration [69] confirmed CL being the source of inhibin during the luteal phase. Studies involving lutectomy in monkeys and other studies in human further confirmed the source of circulating inhibin during the luteal phase in the reproductive cycle [39,40,70]. Subsequent development of sensitive assays and measurement using these assays showed similar pattern of secretion of inhibin A.…”

“…The primate CL is unique, in that along with progesterone (P 4 ) biosynthesis, it also synthesizes substantial amounts of estradiol (E 2 ) and inhibin A isoform. The fact that CL is the major source of inhibin during the luteal phase was confirmed by the observation of rapid decrease in immunoreactive inhibin levels following lutectomy in cynomolgus monkeys and specific inhibin A levels in bonnet monkeys [39,40]. The secretion of inhibin A in CL appears to be regulated by LH, since inhibition of pituitary LH secretion by treatment with gonadotropin releasing hormone receptor (GnRH-R) antagonist caused a rapid decline in circulating inhibin and inhibin-α subunit mRNA levels [40][41][42][43][44].…”

“…The fact that CL is the major source of inhibin during the luteal phase was confirmed by the observation of rapid decrease in immunoreactive inhibin levels following lutectomy in cynomolgus monkeys and specific inhibin A levels in bonnet monkeys [39,40]. The secretion of inhibin A in CL appears to be regulated by LH, since inhibition of pituitary LH secretion by treatment with gonadotropin releasing hormone receptor (GnRH-R) antagonist caused a rapid decline in circulating inhibin and inhibin-α subunit mRNA levels [40][41][42][43][44]. In primates, circulating levels of inhibin A and P 4 manifested concordant changes such that both exhibited rise and fall during the luteal phase and both decreased following lutectomy which confirms the source of inhibin secretion during the luteal phase [39,40,45].…”

“…The secretion of inhibin A in CL appears to be regulated by LH, since inhibition of pituitary LH secretion by treatment with gonadotropin releasing hormone receptor (GnRH-R) antagonist caused a rapid decline in circulating inhibin and inhibin-α subunit mRNA levels [40][41][42][43][44]. In primates, circulating levels of inhibin A and P 4 manifested concordant changes such that both exhibited rise and fall during the luteal phase and both decreased following lutectomy which confirms the source of inhibin secretion during the luteal phase [39,40,45]. Inhibin A biosynthesis in CL appears to be present only in higher primates since expression of inhibin-α subunit has been reported to be turned off following luteinization in rodent and bovine species [46][47][48].…”

The effect of progesterone replacement on gene expression in the corpus luteum during induced regression and late luteal phase in the bonnet monkey (Macaca radiata)

“…Adult female bonnet monkeys ( Macaca radiata ) weighing 3.3-5.1 kg were utilized for the study. The general care and housing of monkeys have been described elsewhere [21]. In this study, one day after occurrence of peak E 2 surge was designated as day 1 of the luteal phase, and CL was collected on designated days of the luteal phase and/or after administration of different treatments (see below).…”