Ontogeny of Cytosolic Androgen Receptors in the Brain of the Fetal Rhesus Monkey*

Abstract

In this study we compared the binding characteristics of methyltrienolone (R1881) in pooled cytosols from the hypothalamus-preoptic area-amygdala-septum (HPAS) of adult and fetal rhesus macaques. In addition, we studied the ontogeny of cytosolic androgen receptors (AR) in fetal neural tissue. Intact adult males and fetal rhesus monkeys of known gestational age were our experimental subjects. Fetuses were delivered by cesarean section at 50, 65, 80, and 150 days gestation. HPAS cytosols from 150-day fetuses and adult males were incubated with the synthetic ligand, [3H]R1881, for determining AR characteristics and to validate the assay. A single high affinity, low capacity receptor for R1881 was found in HPAS cytosols. The apparent dissociation constant was similar between adult and fetal HPAS (1.09 X 10(-10) vs. 1.59 X 10(-10) M, respectively). Binding specificity was determined by the addition of excess radioinert testosterone (T), 5 alpha-dihydrotestosterone, estradiol, or progesterone to the incubation tube. R1881 binding was displaced by the addition of excess amounts of T and dihydrotestosterone, but not of estradiol or progesterone. There were no differences between fetal and adult animals. Single point analyses of AR numbers in fetal animals showed significant age and regional differences (P less than 0.05). Since no sex differences were apparent, data from males and females were combined. In the hypothalamus-preoptic area there was a significant increase in AR throughout gestation [1.3 +/- 0.4 (+/- SE) fmol/mg protein; n = 7 (50 days gestation) vs. 6.2 +/- 0.3 fmol/mg protein; n = 4 (150 days of gestation); P less than 0.01]. These values differed significantly from adult male hypothalamic-preoptic area (14.1 +/- 0.3 fmol/mg protein; P less than 0.01; n = 3). AR levels in frontal and temporal cortex were high on day 50 of gestation, but showed a significant decline by day 150 (P less than 0.05). The administration of testosterone propionate (25 mg/kg.day) to pregnant animals from 40-50 days gestation, which resulted in elevated levels of serum T in female, but not male, fetuses had no effect on AR in any brain region studied. These studies confirm the presence of AR in fetal monkey brain. New information is provided on the changes in AR numbers in cortical and hypothalamic tissues during the critical period for sexual differentiation of the primate brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Binding Sites in Human Temporal Cortex

“…These data reveal that the Kd of [?H] 5a-dihydrotestosterone for the androgen receptor is consis tently in the low nanomolar range (X ± SEM = 2.0 ± 0.5). These values are entirely consistent with previously reported Kd for (JH]5a-dihydrotestosterone in both the rat [14] and primate brain [6,13,19], as well as with data obtained using the syn thetic androgen [3H]RU 1881, as radioligand [6,10], The data reveal some variation in binding capacity (Bm i" values of 36.4-83.4 fmol/mg protein; X ± SEM = 52.1 ± 9.1). This value is very similar to that recently reported for the cortex in a species of old world monkey [vervet monkey, Cercopithecus aeihiops; 13] and higher than that reported in rodent brain [ 10,14], However, estimates of the binding capacity should be quali fied since our samples were obtained from 'intact' males.…”

“…There is now considerable evidence for high affinity androgen receptor sites in the CNS of a wide range of mammalian species, providing a mechanism for direct effects of androgens on neuronal func tions [2,6,7,9,10,13,14,16,17,18,19,26]. In primates in particular, the distribution of androgen receptors is widespread, including a number of limbic structures, midbrain nuclei in volved in sensory processing, and cortical regions [6,13,16,18,25,26], The localization of receptors in cortical areas suggests that androgens might influence higher cognitive processes characteristic of primate species.In the present study we have characterized androgen recep tor binding in human temporal cortex biopsies. Soluble frac tions were prepared from 'fresh' tissue samples that were main tained on ice following surgical removal and frozen within 60 min.…”

Sex Differences in the Brain: Implications for Explaining Autism

“…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).…”

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

“…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].…”

“…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].Fetal development, homeostasis, and mechanisms controlling the timing of parturition are influenced by both circulating and locally-produced steroid hormones [19;20]. We and others have investigated the changes in hormone secretion and action, especially at or near the end of gestation, which prepare the fetus for extrauterine life [2-4;10;21;22].…”