Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 2024
• Main Authors: Šošić-Jurjević, Branka, Ajdžanović, Vladimir, Miljić, Dragana, Trifunović, Svetlana, Filipović, Branko, Stanković, Sanja, Bolevich, Sergey, Jakovljević, Vladimir, Milošević, Verica
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2020; MDPI
• Subjects: Adenoma - pathology; Adrenocorticotropic Hormone - metabolism; Age; Androgens; Angiogenesis; Animals; Cancer; Cell Differentiation; Disease Models, Animal; Dopamine; Enzymes; Estradiol; Estrogens; Estrogens - adverse effects; Female; Females; Genes; Growth factors; Hormones; Humans; Hyperplasia; Hyperplasia - metabolism; Hyperplasia - pathology; Male; Medical prognosis; Mice; Physiology; Pituitary Diseases - metabolism; Pituitary Diseases - pathology; Pituitary gland; Pituitary Gland - metabolism; Pituitary Neoplasms - pathology; Prolactin; Prolactinoma - metabolism; Prolactinoma - pathology; Protein expression; Rats; Review; Sexes; Stem Cells; Thyrotropin - metabolism; Tumor Microenvironment - physiology; Tumors; microenvironment; thyroid-stimulating hormone; estrogen; folliculo-stellate cells; prolactin; prolactinoma; rat; men; pituitary gland; adrenocorticotropic hormone
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21062024

Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature.