Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β‐containing neurons in the mouse hypothalamic paraventricular nucleus

• Published in: Journal of comparative neurology (1911) 2021-06, Vol.529 (9), p.2283-2310
• Main Authors: Contoreggi, Natalina H., Mazid, Sanoara, Goldstein, Lily B., Park, John, Ovalles, Astrid C., Waters, Elizabeth M., Glass, Michael J., Milner, Teresa A.
• Format: Article
• Language: English
• Subjects: Age Factors; androgen receptor; Androgen receptors; Animals; Autonomic nervous system; Dendrites; estrogen receptor alpha; Estrogen Receptor beta - analysis; Estrogen Receptor beta - biosynthesis; Estrogen Receptor beta - ultrastructure; Estrogen receptors; Estrogens; Female; Females; Gonadal Steroid Hormones - analysis; Gonadal Steroid Hormones - biosynthesis; Green fluorescent protein; G‐protein–coupled estrogen receptor; Hypothalamus; Male; Males; menopause; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurons - metabolism; Neurons - ultrastructure; Paraventricular Hypothalamic Nucleus - chemistry; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular Hypothalamic Nucleus - ultrastructure; Paraventricular nucleus; Progestin; progestin receptor; Receptors, Androgen - analysis; Receptors, Androgen - biosynthesis; Receptors, Androgen - ultrastructure; Receptors, G-Protein-Coupled - analysis; Receptors, G-Protein-Coupled - biosynthesis; Receptors, G-Protein-Coupled - ultrastructure; Reproductive status; Sex Characteristics; Sex hormones
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.25093

Within the hypothalamic paraventricular nucleus (PVN), estrogen receptor (ER) β and other gonadal hormone receptors play a role in central cardiovascular processes. However, the influence of sex and age on the cellular and subcellular relationships of ERβ with ERα, G‐protein ER (GPER1), as well as progestin and androgen receptors (PR and AR) in the PVN is uncertain. In young (2‐ to 3‐month‐old) females and males, ERβ‐enhanced green fluorescent protein (EGFP) containing neurons were approximately four times greater than ERα‐labeled and PR‐labeled nuclei in the PVN. In subdivisions of the PVN, young females, compared to males, had: (1) more ERβ‐EGFP neurons in neuroendocrine rostral regions; (2) fewer ERα‐labeled nuclei in neuroendocrine and autonomic projecting medial subregions; and (3) more ERα‐labeled nuclei in an autonomic projecting caudal region. In contrast, young males, compared to females, had approximately 20 times more AR‐labeled nuclei, which often colocalized with ERβ‐EGFP in neuroendocrine (approximately 70%) and autonomic (approximately 50%) projecting subregions. Ultrastructurally, in soma and dendrites, PVN ERβ‐EGFP colocalized primarily with extranuclear AR (approximately 85% soma) and GPER1 (approximately 70% soma). Aged (12‐ to 24‐month‐old) males had more ERβ‐EGFP neurons in a rostral neuroendocrine subregion compared to aged females and females with accelerated ovarian failure (AOF) and in a caudal autonomic subregion compared to post‐AOF females. Late‐aged (18‐ to 24‐month‐old) females compared to early‐aged (12‐ to 14‐month‐old) females and AOF females had fewer AR‐labeled nuclei in neuroendrocrine and autonomic projecting subregions. These findings indicate that gonadal steroids may directly and indirectly influence PVN neurons via nuclear and extranuclear gonadal hormone receptors in a sex‐specific manner. Light and electron microscopic studies reveal that gonadal steroids may directly and indirectly influence PVN neurons via nuclear (a) and extranuclear (b) gonadal hormone receptors in a sex‐specific manner. AR, androgen receptor; ER, estrogen receptor; GPER, G‐protein–coupled estrogen receptor.