Androgen and Estrogen Receptors in Fetal Rhesus Monkey Brain and Anterior Pituitary*

Abstract

In this study, we sought to identify and characterize cytosolic androgen and estrogen receptors in the brain and anterior pituitary gland (AP) of fetal rhesus monkeys using the technique of DNA-cellulose chromatography. Cytosolic extracts were prepared from fetal monkey (days 135-162 of gestation) tissues including hypothalamus-preoptic area/amygdala (HPOA/AMG), cerebral cortex, and AP. Extracts were incubated with [3H]testosterone, [3H]5 alpha-dihydrotestosterone, or [3H] 17 beta-estradiol and applied to DNA-cellulose columns. [3H]Androgen- and [3H]estrogen-binding activities from cytosolic extracts adhered to DNA-cellulose. After elution with a linear salt gradient (10-500 mM NaCl) [3H]androgen-binding activity exhibited elution maxima between 130-150 mM NaCl, while [3H] estrogen-binding activity exhibited elution maxima between 200-220 mM NaCl. These elution patterns were similar in every region examined and were characteristic of putative androgen and estrogen receptors found in other vertebrate species. Additional experiments established the high affinity-low capacity nature of both androgen- and estrogen-binding activities, as well as their inhibition by known competitors of receptor binding. Estimates of binding activity at ligand concentrations that approximated saturation suggested that the concentration (moles specific bound per mg cytosolic protein) of both androgen and estrogen receptor were highest in the AP, intermediate in the HPOA/AMG, and lowest in the cerebral cortex. Comparisons of androgen- and estrogen-binding activities revealed that in the AP, apparent concentrations of the estrogen receptor exceeded those of androgen. Androgen and estrogen receptor concentrations were roughly equivalent in the HPOA/AMG, whereas, in the cerebral cortex, androgen receptor concentration was greater than estrogen. Collectively, these data demonstrate that in the fetal primate brain and AP, distinct androgen and estrogen receptors are present which might mediate the action of gonadal steroids on sexual differentiation.

Spatial function in adolescents and young adults with congenital adrenal hyperplasia: Clinical phenotype and implications for the androgen hypothesis

“…Improved spatial function could reflect an organizational influence of androgens in one or more cognitive brain systems. The parietal cortex is one candidate site because it expresses androgen receptors prenatally (Pomerantz et al, 1985), is reliably implicated in mental rotation (Zacks, 2008), and exhibits prominent sex differences during rotation tasks in functional imaging studies (Thomsen et al, 2000). However, spatial proficiency is affected by training and experience, not innate potential alone.…”

Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary

“…Nevertheless, the results of the present study are consistent with previously reported studies from other laboratories. Previous reports have demonstrated androgen receptor at the protein and receptor binding levels in fetal hypothalamus, hippocampus, and pituitary of the developing rhesus macaque [14][15][16][17]. Androgen receptor binding activity in the rhesus macaque is increased in late gestation compared to mid-gestation [18].…”

Sex Differences in the Brain: Implications for Explaining Autism

“…Detectable levels of enzymes that convert testosterone to its active metabolites are also found in these regions (62). ER-α is found in the hypothalamus and amygdala, with lower concentrations also in the cerebral cortex (63). ARs are present as early as the first trimester, with high expression in temporal cortex and other regions (64).…”