Effects of Estrogen and Progesterone on Pituitary Response to Stimulation by Luteinizing Hormone-Releasing Factor

Abstract

Synthetic LRF in a dose of 150 iig was injected intravenously on two successive days in eight women with secondary amenorrhea. Two of the women received LRF injections only, three were treated with estradiol benzoate (EB) and three were treated with aqueous progesterone (P), each steroid being administered four hours after the start of the first test. Pre-treatment with both steroids had a marked suppressive effect on the magnitude of the pituitary response to exogenous LRF in the second test. The results, suggest a direct effect of ovarian steroids on pituitary gonadotropin producing cells.Ovarian steroids are known to exert both positive and negative feedback effects upon gonadotropin secretion in the human female. Whether this occurs due to direct action on the pituitary, via the hypothalamus, or both, is as yet undetermined. The availability of synthetic LH releasing factor (LRF) has made it possible to investigate the effects of circulating sex steroids on the pituttary response to exogenous LRF, in an attempt to further define their role in the modulation of gonadotropin secretion. In the present study we have investigated the effects of exogenous estradiol benzoate and progesterone on the secretion of gonadotropins by the pituitary following LRF stimulation. MATERIALS AND METHODSEight patients with secondary amenorrhea were included in this study. The amenorrhea was of diverse etiology, but with a minimum of 6 months duration. Studies performed prior to admission routinely included 24 hour-flmine assay for gonadotropins, 17 ketosteroids and 17 hydroxycorticosteroids, x-ray of the sell a turcica, serum gonadotropins, and tests of thyroid function. The patients were hospitalized for the LRF phase of the investigation. Each patient received an. LRF stimulation test on two successive days by administration of 150 jjg of synthetic LRF intravenously. In these patients receiving sex steroids, estradiol benzoate (EB) or progesterone (P) at various dose levels was given by single intramuscular injection 4 hours after the start of the first test. During each LRF stimulation test, control samples were obtained at 15 min. Intervals for one hour before injection of LRF, followed by 10 min. sampling for 60 mins., and 15 min. sampling for 2 hours thereafter. Other samples obtained depended on the dose and type of steroid administered. Serum LH and FSH were measured by specific radioimmunoassays (1,2) and results expressed as mlU/ml serum of 2nd IRP-HMG. The within-assay co-efficient of variation (CV) for six duplicate tubes in each assay was '\-5% and the between assay CV was 2-9%. Estrogen (E2) and progesterone (P) were measured by radioimmunoassay (3,4). All samples from each subject were measured in a single assay. RESULTSTwo patients receiving successive LRF tests without steroid showed a similar response of increased LH secretion in both tests. The response in the second test appeared to be either identical or minimally increased in both patients. The results in one of these cases are shown in Fig. 1. 152 The Endo...

Responsivity of Pituitary Gonadotropes to Luteinizing Hormone-releasing Factor in Idiopathic Precocious Puberty, Precocious Thelarche, Precocious Adrenarche, and in Patients Treated with Medroxyprogesterone Acetate

“…Treatment with combined estrogen and progesterone oral contraceptives lowers both readily releasable LH and FSH (1 1, 40). Short term progesterone treatment in humans also diminishes LRF-induced LH release (40). In several species, in vivo and in vitro studies support the notion that progesterone suppressed the release of pituitary gonadotropins by decreasing hypothalamic LRF release as well as by direct action on the pituitary gonadotropes (7,8,22,36).…”

A Priming Effect of Luteinizing Hormone Releasing Factor on the Anterior Pituitary Gland in the Female Rat

“…The responsiveness of the pituitary gland to LH-RF is consider¬ ably enhanced in patients with hypergonadotrophic hypogonadism (Roth, Kelch, Kaplan & Grumbach, 1972;Gual, 1973;Isurugi, Wakabayashi, Fukutani, Takayasu, Tamaoki & Okada, 1973;Siler & Yen, 1973) and is lowered in prepubertal males and in some, but not all, patients with hypogonadotrophic hypogonadism (Roth et Thompson, Arfania & Taymor (1973) and Roth, Kelch, Kaplan & Grumbach (1973) in their investigations of women with secondary amenorrhoea and children before and at puberty, respectively. It is of interest that in adult male subjects given three successive injections of 25 /¿g LH-RF at intervals of 60 min the concentrations of LH after the second and third injections are greater than after the first injection, although the three increments in LH do not seem to be appreciably different from each other (Wagner, Böckel, Hrubesch & Grote, 1973).…”

Responsivity of Pituitary Gonadotropes to Luteinizing Hormone-releasing Factor in Idiopathic Precocious Puberty, Precocious Thelarche, Precocious Adrenarche, and in Patients Treated with Medroxyprogesterone Acetate

“…When estradiol levels in plasma are raised either by a single intramuscular injection (40) or by a 12-hr infusion (19) of 17P-estradiol, both LH and FSH response to LRF are diminished. In contrast, treatment for 6 days with 17P-estradiol enhanced pituitary gonadotropin release after LRF (20).…”