Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

Abstract

Sex steroid hormones, such as androgens and estrogens, are known to exert organizational action at perinatal periods and activational effects during adulthood on the brain and peripheral tissues. These organizational effects are essential for the establishment of biological axes responsible for regulating behaviors, such as reproduction, stress, and emotional responses. Estradiol (E2), testosterone, and their metabolites exert their biological action through genomic and non-genomic mechanisms, bounding to canonical receptors, such as estrogen receptor (ER)α, ERβ, and androgen receptor (AR) or membrane receptors, such as the G protein-coupled estrogen receptor (GPER), respectively. Expression of ERs and AR was found to be different between males and females both in the brain and peripheral tissues, suggesting a sex-dependent regulation of their expression and function. Therefore, studying the ERs and AR distribution and expression levels is key to understand the central and peripheral role of sex steroids in the establishment of sex-specific behaviors in males and females. We investigated the organizational effects of estrogens and androgens in the pituitary and adrenal glands of adult male and female rats. For this, selective blockade of AR with flutamide or 5α-reductase with finasteride or aromatase with letrozole during the first 5 days of life has been performed in male and female pups and then quantification of ERs and AR expression in both glands has been carried out in adulthood. Data show that inhibition of dihydrotestosterone (DHT) and E2 production during the first five postnatal days mainly decreases the ER expression in male to female values and AR expression in female to male levels in the pituitary gland and increases AR expression in female to male levels in the adrenal gland. In contrast, blocking the action of androgens differentially modulates the ERs in males and females and decreases AR in both males and females in both glands. Altogether, the results suggest that neonatal modifications of the androgen and estrogen pathways can potentially lead to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes.

Is membrane androgen and estrogen receptor signaling imperative in the governing function of the adrenal cortex in the Eurasian beaver (Castor fiber L.)?

“…There are poor number of studies, including ours, reported regulatory roles and/or mutual interactions of adrenal estrogen signaling through both canonical and noncanonical estrogen receptors for males (Lagunas et al, 2022; Pacwa et al, 2018; Pawlicki et al, 2023; Trejter et al, 2015). Pharmacological blockage of androgen and GPER estrogen signaling leads to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes (Lagunas et al, 2022). Also, membrane sex receptor signaling is sensitive to environmental androgen and estrogen‐like compounds which nowadays pollute water, land, and air environments (Amir et al, 2021).…”

“…In feminizing adrenal tumors, the mechanism of estrogen production has been proposed to be due to either peripheral aromatization of androgens or estrogen production from the tumor itself (Phornphutkul et al, 2001). There are poor number of studies, including ours, reported regulatory roles and/or mutual interactions of adrenal estrogen signaling through both canonical and noncanonical estrogen receptors for males (Lagunas et al, 2022;Pacwa et al, 2018;Pawlicki et al, 2023;Trejter et al, 2015). Pharmacological blockage of androgen and GPER estrogen signaling leads to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes (Lagunas et al, 2022).…”

The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor

“…Whether estrogen-mediated aldosterone synthesis through ERβ is reconciled with the fact that healthy premenopausal women have higher serum aldosterone levels compared to healthy men of the same age through GPER activity, cannot be assured. It has been described, that in the adrenal glands, unlike the pituitary, GPER expression is not sexually dysmorphic [ 41 , 43 ].…”

Effects of Nonylphenol on the Secretion of Catecholamines and Adrenocortical Hormones from Short-Term Incubated Rat Adrenal Glands

“…Mainstream of research on the endocrine disrupting chemicals (EDCs) has been reproductive toxicity, which is about the adverse effects of sex steroid-like substances on the hypothalamic-pituitary-gonadal (HPG) hormone axis and its target organs ( Czarnywojtek et al, 2023 ). Since mammalian adrenal glands have steroid receptors, and share a high similarity with gonads in synthesize and secrete steroid hormones from cholesterol, the glands could be suitable for research on EDCs ( Hinson & Raven, 2006 ; Lagunas et al, 2022 ). In fact, EDC studies on the adrenal gland have been gradually accumulating, although in much smaller amounts than on the gonads; these are including adrenal steroidogenesis disruption by diethylstilbestrol (DES) ( Haeno et al, 2015 ), genistein-induced histomorphometric and hormone secreting changes in the adrenal cortex ( Ajdžanović et al, 2009 ), corticosterone secretion changes by low-dose bisphenol-A ( Lan et al, 2015 ), reduced pubertal development of cortex by triphenyltin chloride ( Li et al, 2020 ), and disruption of cortical function by dipentyl phthalate ( Chen et al, 2023 ).…”