Rein M S, Friedman A J, Heffner L J
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Endocrinol Metab. 1990 Jun;70(6):1554-8. doi: 10.1210/jcem-70-6-1554.
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.
子宫内膜、子宫肌层和子宫平滑肌瘤（纤维瘤）均分泌催乳素（PRL）。尽管对子宫内膜PRL分泌的调节已进行了广泛研究，但对子宫肌层和纤维瘤PRL的了解却很少。本研究调查了体内给予促性腺激素释放激素激动剂（GnRH-a）醋酸亮丙瑞林缓释剂对外植体培养的纤维瘤和子宫肌层PRL分泌的影响。组织取自17名参与一项前瞻性、随机、双盲、安慰剂对照临床试验的患者。在特定的无血清培养基中建立纤维瘤和子宫肌层的外植体培养，并对收获的培养基进行PRL和总蛋白检测。纤维瘤PRL分泌显著高于子宫肌层PRL分泌。纤维瘤PRL分泌随时间增加，而子宫肌层PRL分泌则不然。与对照组相比，GnRH-a治疗患者的纤维瘤PRL分泌显著降低，但子宫肌层PRL分泌未受影响。体内给予GnRH-a对纤维瘤蛋白分泌无影响。体外补充孕酮可抑制纤维瘤PRL分泌；体外雌激素和GnRH-a的影响极小。蛋白质印迹分析显示，纤维瘤分泌的PRL中有一小部分是糖基化的。这些结果表明：1）纤维瘤的PRL分泌高于子宫肌层；2）体内用GnRH-a治疗24小时后，体外纤维瘤PRL分泌特异性降低；3）体外雌激素或孕酮不能逆转体内给予GnRH-a的抑制作用；4）体外GnRH-a对纤维瘤PRL分泌无影响。
