Direct inhibitory effect of estradiol on pituitary luteinizing hormone responsiveness to luteinizing hormone releasing hormone is specific and of rapid onset.
We have employed a perifusion technique to explore the time course and specificity of 17 beta-estradiol (E2) effects directly upon luteinizing hormone (LH) release from the isolated rat anterior pituitary under pulsatile luteinizing hormone releasing hormone (LHRH) stimulation. We first characterized the perifusion system and fitted the data to a simple dose-response model. Multiple perifusion studies were then performed with pulses of LHRH at approximately half-maximal response concentration (10(-8) M); LH responses to an initial LHRH pulse (#1) were compared with LH responses to a second LHRH pulse (#2) given at variable times after addition of E2, antiestrogen (LY 117018), and/or 17 alpha-estradiol (17 alpha-E2). Using this approach, we found that the direct inhibitory effect of E2 upon LH responsiveness to LHRH was rapid and specific. The ratio of LH secretion in response to LHRH pulse #2 to that in response to LHRH pulse #1 (LH secretion ratio) decreased steadily during 1 h of exposure to E2. This inhibition was significant (P less than 0.01) by 36 min of E2 exposure. It represented more than the removal of a LHRH self-priming effect because the LH secretion ratios were significantly less than 1.0 [0.80 +/- 0.05 (SEM), P less than 0.01] within 36 min of E2 exposure. The inhibitory effect was not seen when LY 117018 was added with E2, nor when 17 alpha-E2 replaced E2. The specificity of this rapid E2 inhibitory effect upon pituitary LH responsiveness to LHRH strongly suggests that it is receptor mediated. The rapidity of this apparent receptor-mediated estrogen effect suggests that it is a very rapid consequence of nuclear translocation of the E2-receptor complex.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010477:Perfusion; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone