Sex And Age Influence Gonadal Steroid Hormone Receptor Distributions Relative To Estrogen Receptor Beta-Containing Neurons In The Mouse Hypothalamic Paraventricular Nucleus

Within the hypothalamic paraventricular nucleus (PVN), estrogen receptor (ER) beta 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 ER beta with ER alpha, 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, ER beta-enhanced green fluorescent protein (EGFP) containing neurons were approximately four times greater than ER alpha-labeled and PR-labeled nuclei in the PVN. In subdivisions of the PVN, young females, compared to males, had: (1) more ER beta-EGFP neurons in neuroendocrine rostral regions; (2) fewer ER alpha-labeled nuclei in neuroendocrine and autonomic projecting medial subregions; and (3) more ER alpha-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 ER beta-EGFP in neuroendocrine (approximately 70%) and autonomic (approximately 50%) projecting subregions. Ultrastructurally, in soma and dendrites, PVN ER beta-EGFP colocalized primarily with extranuclear AR (approximately 85% soma) and GPER1 (approximately 70% soma). Aged (12- to 24-month-old) males had more ER beta-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.