title: Gonadotropin-releasing hormone antagonists attenuate estrogen/progesterone-induced hyperprolactinemia in monkeys.
abstract: Previous studies have documented that exogenous gonadotropin-releasing hormone (GnRH) stimulates prolactin (PRL) secretion and augments thyrotropin-releasing hormone-induced PRL release. Further, the concomitant pulsatile release of PRL and luteinizing hormone (LH) suggests that GnRH may be an important regulator of PRL release in certain physiologic states. The authors explored this possibility by evaluating the effect of a GnRH antagonist ([Ac-pClPhe1, pClPhe2, DTrp3, DAla10]-GnRH; GnRH-antagonist) on PRL secretion in monkeys with induced hyperprolactinemia. Monkeys were given estradiol (E2) benzoate 25 mg/kg intramuscularly (IM) on cycle days 1 to 28, and a 3-cm progesterone (P) silastic capsule was placed on cycle day 15 and removed on day 28. On cycle days 15 to 28, monkeys were given IM injections of 1 mg/kg GnRH-antagonist (n = 3), 2 mg/kg GnRH-antagonist (n = 3), or vehicle (n = 3). Daily blood samples were assayed for E2, P, and PRL. The degree of PRL elevation was calculated as percent increase in area under the curve for days 15 to 28 when compared with days 1 through 14 (baseline). Luteinizing hormone levels were calculated similarly. Results indicate a dose-dependent effect of GnRH-antagonist on PRL secretion, with the larger dose producing a significantly lower hyperprolactinemic response, as well as a decline in LH. Thus, GnRH-antagonist attenuates induced hyperprolactinemia in a dose similar to that which suppresses LH release. These findings suggest that GnRH is a physiologic regulator of pituitary PRL secretion. In addition, GnRH analogs may be of benefit in controlled ovarian hyperstimulation by attenuating gonadotropin-induced hyperprolactinemia, thereby reducing potential adverse effects on fertility.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas 78284-7836.
authors.forename: D L
authors.initials: DL
authors.lastname: Olive
authors.forename: V
authors.initials: V
authors.lastname: Sabella
authors.forename: R M
authors.initials: RM
authors.lastname: Riehl
authors.forename: R S
authors.initials: RS
authors.lastname: Schenken
authors.forename: A
authors.initials: A
authors.lastname: Moreno
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D011374:Progesterone / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D012016:Reference Values
chemical_list: D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D011388:Prolactin; D007986:Luteinizing Hormone