Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist.
Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion.
Rein
M S
MS
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Friedman
A J
AJ
Heffner
L J
LJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism*; D016729:Leuprolide; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D011388:Prolactin; D016729:Leuprolide