Acute Modulation of Pituitary Gonadotrophin Secretion by Oestradiol or Testosterone in Healthy Men

Abstract

Synthetic luteinizing hormone releasing hormone (LH-RH) provides a useful tool for the study of pituitary regulation in the hypothalamo-adenohypophysialgonadal system. Negro-Villar, Orias & McCann (1973) showed that oestradiol-17\g=b\ given 2 h before injection of LH-RH to ovariectomized rats reduced luteinizing hormone (LH) release. In male dogs, Jones & Boyns (1974) have found that oestradiol-17\g=b\ or diethylstilboestrol similarly reduces LH release in response to LH-RH given 2\m=.\5 h, but not 24 h later. Androgens were without effect in that study.We now report the gonadotrophin responses to LH-RH in healthy men 2 h after i.m. injection of either oestradiol benzoate (2 mg in 1 ml ethyl oleate), testosterone propionate (5 mg in 1 ml ethyl oleate), or with no acute steroid pretreatment.Five men volunteered for these ambulatory studies. They were 20-35 years old, had no history of endocrine disorders and were not taking medication.At least 2 weeks elapsed between experiments. Blood was taken by venepuncture, separated, and stored frozen until assayed for LH and follicle-stimulating hormone (FSH) by radioimmunoassays which have been described previously (Groom, Groom, Cooke & Boyns, 1971). The initial blood sample was always taken between 09.15 and 10.00 h. After two more samples had been removed at hourly intervals, LH-RH (100 µg in sterile water) was injected i.m. and sampling continued every 30 min for 4-5 h.Gonadotrophin responses were calculated as mean ± s.e.m. after first normalizing the data for each man, by expressing hormone concentration as a fraction of the average level within an experiment, and then scaling to make the initial sample mean equal to 100. Significance of the difference between means was given by twotailed Student's i-test.Plasma concentrations of both LH and FSH were raised by LH-RH (Fig. 1). Administration of testosterone 2 h before LH-RH was given, reduced both the LH response (2P < 0-02) and the FSH response (2P < 0-01); oestradiol-17/? reduced the LH response still further (2 < 0-001 v. testosterone; 2 < 0-001 v. control).The effect of acute oestradiol-17/? pretreatment on FSH secretion was variable. In three men, the response was the same as in the control experiment (2 > 0-98) over the period 0-1 h after LH-RH injection; the other two men showed no stimu¬ lation of FSH release. The latter belonged to a group of three who had wives in the

Effect of Luteinizing Hormone Releasing Hormone on Plasma Levels of Luteinizing Hormone, Oestradiol and Testosterone in the Male Dog

“…In relation to this, it has been reported that oestradiol-17/? inhibits luteinizing hormone re¬ leasing hormone (LH-RH)-induced LH release in men (Cole, Llewelyn, Link & Boyns, 1974) and in male dogs (Jones & Boyns, 1974). The inhibitory effect can be observed with i.v.…”

Inhibition by Oestradiol of the Pituitary Response to Luteinizing Hormone Releasing Hormone in the Dog

“…However, it has been reported (Debeljuk, Arimura & Schally, 1972; Debeljuk, Vilchez-Martinez, ) that pretreatment of the male rat with oestradiol benzoate may either augment LH release induced by LH-RH or partially suppress the response. Furthermore, in man, Cole et al (1974) found that pretreatment with 2 mg oestradiol benzoate, 2 h before the injection of LH-RH, blocked LH release, whereas studies in female rats , in sheep (Reeves et al 1971) and in women (Kastin, Schally, Guai, Midgley, Bowers & Diaz-Infante, 1969) have indicated that small doses of oestrogen may increase the LH response to LH-RH. VilchezMartinez, , however, showed that pretreatment of the dioestrous rat with oestradiol 2-6 h before administering LH-RH, inhibited the pituitary response.…”

“…Intravenous injections of luteinizing hormone releasing hormone (LH-RH) produce an immediate increase in plasma concentrations of LH in many species, including the dog (Reeves, Arimura & Schally, 1971;Boyns, Jones, Bell, Christie & Parkes, 1972) while oestradiol-17/? inhibits the pituitary response to LH-RH (Negro-Villar, Orias & McCann, 1973;Cole, Llewelyn, Link & Boyns, 1974;Jones & Boyns, 1974). In the dog, this effect was elicited 2-5 h but not 24 h after administering the oestrogen (Jones & Boyns, 1974).…”