Sex differences in the distribution of androgen receptors in the human hypothalamus

Abstract

The present study reports for the first time the distribution of androgen receptor immunoreactivity (AR-ir) in the human hypothalamus of ten human subjects (five men and five women) ranging in age between 20 years and 39 years using the antibody PG21. Prolonged postmortem delay (72:00 hours) or fixation time (100 days) did not influence the AR-ir. In men, intense nuclear AR-ir was found in neurons of the horizontal limb of the diagonal band of Broca, in neurons of the lateromamillary nucleus (LMN), and in the medial mamillary nucleus (MMN). An intermediate nuclear staining was found in the diagonal band of Broca, sexually dimorphic nucleus of the preoptic area, paraventricular nucleus, suprachiasmatic nucleus, ventromedial nucleus, and infundibular nucleus, whereas weaker labeling was found in the bed nucleus of the stria terminalis, medial preoptic area, dorsal and ventral zones of the periventricular nucleus, supraoptic nucleus, and nucleus basalis of Meynert. In most brain areas, women revealed less staining than men. In the LMN and the MMN, a strong sex difference was found. Cytoplasmic labeling was observed in neurons of both sexes, although women showed a higher variability in the intensity of such staining. However, no sex differences in AR-ir were observed in the bed nucleus of the stria terminalis, the nucleus basalis of Meynert, or the islands of Calleja. Species differences and similarities of the AR-ir distribution are discussed. The present results suggest the participation of androgens in the regulation of various hypothalamic processes that are sexually dimorphic.

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

“…As a rule, AR is found throughout the hypothalamus and preoptic area as well as in telencephalic structures that project to these regions. Indeed, AR is found in the same structures investigated here (BST, PVN, VMH, MeA, and PMv) in diverse mammalian species including (but not limited to) rats, mice, hamsters, ferrets, opossums, sheep, and humans (e.g., Clancy et al, 1994;Fernández-Guasti et al, 2000;Herbison et al, 1996;Iqbal et al, 1995;Kashon et al, 1996;Lu et al, 1998;Simerly et al, 1990;Wood and Newman, 1995). The BST, PVN, MeA, VMH, and PMv comprise key nodes of an interconnected neural circuit that regulates neuroendocrine function and couples the expression of reproductive behaviors with appropriate environmental stimuli.…”

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

“…In addition, a sex difference in AR staining was present in the horizontal diagonal band of Broca, SDN-POA, medial preoptic area (MPO), dorsal and ventral zone of the periventricular nucleus (PVN), supraoptic nucleus (SON), ventromedial hypothalamic nucleus, and infundibular nucleus (INF). However, no sex differences were observed in AR staining in the adult bed nucleus of the stria terminalis (BST), the nucleus basalis of Meynert, and the islands of Calleja (73). No differences related to male sexual orientation were found in nuclear AR activity in the mamillary complex, this activity not being found to differ in heterosexual men compared with homosexual men, but it was significantly stronger than in women.…”

“…The strongest sex difference was found in the lateral and the medial mamillary nucleus (MMN; 73). The mamillary body complex is known to be involved in several aspects of sexual behavior, such as arousal of sexual interest and penile erection (58,73,74). In addition, a sex difference in AR staining was present in the horizontal diagonal band of Broca, SDN-POA, medial preoptic area (MPO), dorsal and ventral zone of the periventricular nucleus (PVN), supraoptic nucleus (SON), ventromedial hypothalamic nucleus, and infundibular nucleus (INF).…”

Biochemical and molecular studies using human autopsy brain tissue

“…In analyses of the effect of gender on expression, significantly lower levels of mRNA transcripts of the serotonin receptor genes 1E and 5 A, the dopamine D5 receptor gene and the neurone-specific enolase gene have been found in males (Castensson et al 2002). Higher dopamine and serotonin transporter availabilities have been found by positron emission tomography in females (Staley et al 2001;Zubieta et al 2002), and gender differences in androgen receptor expression in hypothalamus and the mammillary bodies have been reported (Fernandez-Guasti et al 2000;Kruijver et al 2001). Higher l-opioid binding in women has been observed in a number of cortical and subcortical areas (Zubieta et al 1999), and differences between the genders in the concentrations of small-MW metabolites have also been noted (Konradi et al 1992;Grachev and Apkarian 2000a,b).…”