Reduction in Pituitary Desensitization and Prolongation of Gonadotropin Release by Estrogen during Continuous Administration of Gonadotropin-Releasing Hormone in Women: Its Antagonism by Progesterone*

Abstract

The present study was designed to elucidate gonadal steroid influences on gonadotropin release and subsequent pituitary desensitization to GnRH. Sixteen women, 10 of whom were normal and 6 of whom had hypogonadism, were infused with GnRH at rates ranging from 0.313-10 micrograms/h via an indwelling iv catheter for 66 h. Blood samples obtained throughout the GnRH infusion were analyzed for LH, FSH, estradiol, and progesterone. A prompt and substantial release of gonadotropin occurred in women with ovarian failure or during the luteal phase in normal women compared with that during the follicular phase of the menstrual cycle. Thereafter, a gradual decrease in gonadotropin secretion occurred due to pituitary desensitization, which was slower in the follicular phase than in other groups. A dose-related increase in integrated LH release occurred during GnRH infusion, but this response tapered off with administration of large doses of GnRH to women with ovarian failure or during the luteal phase. In contrast, it increased linearly up to the maximum dose of GnRH in the follicular phase. These data suggest that 1) basal levels of estrogen suppress the early rapid release of gonadotropin in response to GnRH and reduce subsequent pituitary desensitization, resulting in the prolonged release of LH; 2) estrogen widens the range of dose-related increases in gonadotropin in response to GnRH; and 3) these effects of estrogen are antagonized by progesterone.

Effects of constant infusion of gonadotrophin-releasing hormone in ovariectomized ewes with hypothalamo-pituitary disconnection: further evidence for differential control of LH and FSH secretion and the lack of a priming effect

“…In rats oestrogen enhances the self-priming effect of GnRH (Aiyer, Chiappa & Fink, 1974) by acting on the pituitary and by increasing endogenous GnRH release (Speight, Popkin, Watts & Fink, 1981). Araki, Chikazawa, Motoyama et al (1985) found that pitui¬ tary desensitization during high-dose infusions of GnRH is less marked during the oestrogen-dominant, follicular phase of the menstrual cycle in women.…”

Actions of gonadotropin-releasing hormone analogues in pituitary gonadotrophs and their modulation by ovarian steroids

“…This might be due to a more distinct depletion of LH pool by triptorelin and the additional steroid treatment. Araki et al suggested that estradiol reduces pituitary desensitization and that the effects of estradiol are antagonized by progesterone [55]. Simard et al demonstrated that progesterone potentiates the inhibitory effect of estradiol on LH mRNA levels in male and female rats stimulated with triptorelin [56].…”

Can GnRH agonists act directly on the ovary and contribute to cyst formation?

“…This is attributed to the ability 1991; Parinaud et al, 1992;Jenkins et al, 1993). of progesterone to decrease gonadotrophin release in response There have been several reports on the presence of ovarian to GnRH agonist (Araki et al, 1985), therefore the initial cysts while the women are still undergoing treatment with transient 'flare-up effect' of GnRH agonist becomes subdued GnRH agonists (Feldberg et al, 1989;Ron-El et al, 1989; and subsequently the formation of cysts. This hypothesis Sampaio et al, 1991;Jenkins et al, 1992;Parinaud et al, explains the presence or formation of ovarian cysts after GnRH 1992; Stewart et al, 1992;Jenkins et al, 1993;Tarlatzis et al, agonist administration, but fails to explain how these 'cysts' 1994; Keltz et al, 1995;Weissman et al, 1998).…”