The importance of luteinizing hormone in the control of inhibin and progesterone secretion by the human corpus luteum.
Serum inhibin levels rise markedly during the luteal phase of the human menstrual cycle and are closely correlated with serum progesterone (P) levels, suggesting that the corpus luteum (CL) secretes inhibin. While FSH is the major regulator of inhibin secretion by the granulosa cells, the control of CL inhibin secretion is unclear. We hypothesized that, like P, CL inhibin secretion would be LH dependent. To examine this possibility, normal women were given the GnRH antagonist [Ac-D2Nal1, D4CL Phe2, D3Pal3, Arg5, DGlu6 (AA), DAla10]GnRH (Nal-Glu antagonist) for 3 consecutive days commencing on day 6-8 of the luteal phase. The daily doses were 2.5 (n = 3), 10 (n = 4), and 25 micrograms/kg (n = 5), sc. Serum LH levels fell 2 h after injection, and the fall was maximal (70-74%) at 6 h; the degree of suppression was not dose dependent. The duration of suppression was dose related, being less than 12 h, between 12, and 24 h, and more than 24 h for the 2.5, 10, and 25 micrograms/kg doses, respectively. Serum FSH levels declined by 22-43%, but the effect was not dose related. Serum P levels fell by 42-45% 8 h after each dose of antagonist. They returned to baseline 24 h after the 2.5 micrograms/kg dose, but after both the 10 and 25 micrograms/kg doses serum P levels continued to fall, and menstrual bleeding commenced within 48-72 h after the first antagonist injection. Serum inhibin levels were not altered relative to normal cycles by the 2.5 micrograms/kg dose, but fell by 48% and 58%, and 62% and 73% respectively, 48 and 72 h after the 10 and 25 micrograms/kg doses, respectively. Serum P and inhibin levels correlated closely in all women. To examine the relative roles of FSH and LH in the control of CL function, Nal-Glu antagonist (25 micrograms/kg, sc) was administered at 0 and 24 h commencing on day 6-8 of the luteal phase, in combination with either human menopausal gonadotropin (hMG; 150 IU, im, every 12 h) or hCG (1500 IU, im, once), both commencing at 0 h. hMG administration led to a rapid (by 2 h) and marked (3- to 9-fold) rise in serum FSH levels, whereas serum LH remained low, similar to antagonist alone treatment cycless.(ABSTRACT TRUNCATED AT 400 WORDS)
McLachlan
R I
RI
Department of Medicine, University of Washington, Seattle 98195.
Cohen
N L
NL
Vale
W W
WW
Rivier
J E
JE
Burger
H G
HG
Bremner
W J
WJ
Soules
M R
MR
D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage*; D003338:Corpus Luteum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D008596:Menotropins / Q000008:administration & dosage; D010905:Pituitary Hormone Release Inhibiting Hormones / Q000008:administration & dosage; D011374:Progesterone / Q000097:blood / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D010905:Pituitary Hormone Release Inhibiting Hormones; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007265:Inhibins; D008596:Menotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone