The permissive role of prolactin as a regulator of luteinizing hormone action in the female mouse ovary and extragonadal tumorigenesis

Author:

Bachelot Anne12,Carré Nadège34,Mialon Olivier34,Matelot Melody34,Servel Nathalie5,Monget Philippe6,Ahtiainen Petteri7,Huhtaniemi Ilpo78,Binart Nadine34

Affiliation:

1. AP-HP, Endocrinology and Reproductive Medicine, Pitié-Salpêtrière Hospital, Paris, France;

2. Université Pierre et Marie Curie, Site Pitié, Paris, France;

3. Université Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S693, Paris-Sud, France;

4. INSERM U693, 94276 Kremlin-Bicêtre, France;

5. INSERM U845, Paris, France;

6. INRA, UMR85, Physiologie de la Reproduction et des Comportements, Nouzilly, France;

7. Department of Physiology, University of Turku, Turku, Finland; and

8. Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom

Abstract

Transgenic female mice overexpressing the hCGβ subunit (hCGβ+) and producing elevated levels of luteinizing hormone (LH)/hCG bioactivity present as young adults with enhanced ovarian steroidogenesis, precocious puberty, and infertility. They subsequently develop pituitary prolactinomas, high circulating prolactin (PRL) levels, and marked mammary gland lobuloalveolar development followed by adenocarcinomas. None of these phenotypes appear in gonadectomized mice, indicating that the hCG-induced aberrations of ovarian function are responsible for the extragonadal phenotypes. PRL receptor-deficient (PRLR−/−) female mice are sterile, despite ovulating, due to a failure of embryo implantation, as a consequence of decreased ovarian LH receptor (Lhcgr) expression and inadequate corpus luteum formation and progesterone production. To study further the presumed permissive role of PRL in the maintenance of gonadal responsiveness to LH/hCG stimulation, we crossed the hCGβ+ and PRLR−/− mice. The double-mutant hCGβ+/PRLR−/− females remained sterile with an ovarian phenotype similar to PRLR−/− mice, indicating that LH action, Lhcgr expression, and consequent luteinization are not possible without simultaneous PRL signaling. The high frequency of pituitary prolactinomas in PRLR−/− mice was not affected by transgenic hCGβ expression. In contrast, none of the hCGβ+/PRLR−/− females showed either mammary gland lobuloalveolar development or tumors, and the increased mammary gland Wnt-5b expression, possibly responsible for the tumorigenesis in hCGβ+ mice, was absent in double-mutant mice. Hence, high LH/hCG stimulation is unable to compensate for missing PRL signaling in the maintenance of luteal function. PRL thus appears to be a major permissive regulator of LH action in the ovary and of its secondary extragonadal effects.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

Cited by 13 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3