[³H]Estradiol and Its Metabolites in the Brain, Pituitary Gland, and Reproductive Tract of the Male Rhesus Monkey

Abstract

Previous studies have shown that [³H]estradiol is the major nuclear metabolite of [³H]testosterone in the hypothalamus, preoptic area and amygdala of the male rhesus monkey, and it has been proposed that some of the stimulatory effects of testosterone on male sexual behavior may be mediated by estradiol-concentrating neurons. To map these neurons and identify metabolites, 4 castrated male rhesus monkeys were each injected with 0.47 mCi/kg [³H]estradiol, and the brains were removed 60 min later. Left halves were frozen for thaw-mount autoradiography, and right halves were used to isolate cell nuclei from different brain regions. A fifth animal was used to validate the methodology. Radioactive steroids were identified and measured by high performance liquid chromatography. Brain areas previously shown to contain labeled neurons after [³H]testosterone administration were also labeled after [³H]estradiol, including medial preoptic nucleus (n.), anterior hypothalamic area, bed n. of stria terminalis, ventromedial n., premammillary n., and corticomedial amygdala. Some areas not labeled after [³H]testosterone were labeled after [³H]estradiol, including lateral septal n., arcuate n., paraventricular n., claustrum, entorhinal cortex, and spinal cord. The pars distalis of the pituitary gland was heavily labeled. Most (83%) of the radioactivity in cell nuclei was [³H]estradiol while [³H]estrone was a major metabolite (25%) in supernatants. In the brain, the highest nuclear concentration of [³H]estradiol was in the hypothalamus (249.2 ± 20.0 fmol/mg DNA), although in the previous experiments with [³H]testosterone, the highest nuclear concentrations of [³H]estradiol were found in the amygdala. We interpret these results to indicate that local metabolic differences in the brain may underlie some of the different behavioral effects of gonadal steroids in primates.

Distribution of Estrogen Receptor-Immunoreactive Cells in Monkey Hypothalamus: Relationship to Neurones Containing Luteinizing Hormone-Releasing Hormone and Tyrosine Hydroxylase

“…The distribution of ER-immunoreactive neurones re ported here is in good agreement with a previous receptor autoradiography study in the female rhesus macaque [8] and findings in the male of the same species [9]. Like oth er mammalian species [4-7, 10-12, 15, 25-29], ERimmunoreactive cells in the monkey are concentrated in the POA, BNST and basal hypothalamus.…”

“…Although the distribution of estrogen-concentrating cells in the hypothalamus of the primate has been deter mined in both the male and female rhesus monkey [8,9], the relationship of cells possessing ERs to 'final output' neuroendocrine neurones is not known. In the case of the luteinising hormone-releasing hormone (LHRH) neu rones, evidence that these cells do not possess ERs has accumulated for both female [3] and male [4] rats as well as the guinea pig [10] and ewe [11,12].…”

Effects of Testosterone and Aromatase Inhibition on Estrogen Receptor-Like Immunoreactivity in Male Rat Brain

“…In this respect its properties differed markedly from those of the H222 antibody because the ER-715 antibody appeared to label neurons independently of the treat ment condition. Its labeling distribution was largely re stricted to regions previously shown by autoradiography to contain ER [18][19][20][21][22][23], but labeling was more wide spread than that produced by the H222 antibody. In addition to regions labeled by the H222 antibody, the ER-715 antibody also labeled hippocampal pyramidal neurons and neurons in the caudal-ventrolateral VMH, the arcuate nucleus, and the tuberoinfundibular hypo thalamus.…”

“…In all four castrates, ERir-labeled neurons occurred in LS, BST, POM, StHYP, the anterior, cortical and medial AMG, and several hypo thalamic nuclei including the paraventricular nucleus (PAV), the anterior hypothalamus (AH), and rostral por tions of VMH. However, H222 ERir labeling was more variable in the more caudal regions studied, such as the caudal-ventrolateral VMH, ARC, and the tuberoinfundibular hypothalamus; areas which have previously been shown by autoradiography to contain ER [18][19][20][21][22][23]. Fig ure 2 shows photomicrographs of H222 ERir nuclear neu ronal labeling in (a) POM and (b) StHYP from a castrated male.…”

Intracerebral Infusion of an Aromatase Inhibitor, Sexual Behavior and Brain Estrogen Receptor-Like Immunoreactivity in Intact Male Rats

“…The H222 ERir label ing was almost exclusively confined to neuronal nuclei, as shown for the castrated male in figure 6A of BST and fig ure 7A of POM and, in all 4 animals, it occurred in the lateral septum, BST, POM, striohypothalamic nucleus, the anterior, cortical and medial amygdala, and several hypothalamic nuclei including the paraventricular nu cleus, the anterior hypothalamus, and rostral portions of the ventromedial hypothalamus (VMH). However, H222 ERir labeling was more variable in the more caudal regions studied, such as the caudal-ventrolateral VMH, arcuate nucleus, and the tuberoinfundibular hypothala mus; areas which have previously been shown by autora diography to contain ER [30][31][32][33][34][35].…”