Cellular Observations and Hormonal Correlates of Feedback Control of Luteinizing Hormone Secretion by Testosterone in Long-Term Castrated Male Rhesus Monkeys1

Abstract

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.

Review on testicular development, structure, function, and regulation in common marmoset

“…In castrated adult male marmosets, after a single s.c. injection of 35 μg estradiol benzoate, plasma levels of LH initially decreased within the first 4–12 hr and then increased abruptly between 12–24 hr, with maximal LH levels occurring at about 24 hr after injection (Hodges and Hearn, 1978). This pattern of negative‐positive feedback in LH response to estradiol injection in castrated marmosets is similar to those observed in castrated males of other mammals (e.g., rhesus monkeys) (Steiner et al, 1976; Resko et al, 2000). In the intact adult male, the majority of the animals demonstrated an initial decrease and then increase in LH levels after estradiol administration.…”

Brain and cognition abnormalities in long-term anabolic-androgenic steroid users

“…Hypogonadism could lead not only to persistently reduced systemic testosterone and estrogen levels, but also to reduced aromatase activity in some brain areas (Resko et al, 2000). In turn, brain aromatase activity reductions could reduce brain-derived estrogen levels, compromise neuroprotection (Liu et al, 2014; Veiga et al, 2005), and enhance AAS-amplified neurotoxicity (Orlando et al, 2007).…”

Endocrine Antecedents of Polycystic Ovary Syndrome in Fetal and Infant Prenatally Androgenized Female Rhesus Monkeys1

“…Our present findings in PA females emulate this LH differential: Specifically, fetal PA females, when exposed to testosterone levels typical of those seen in the lower range of normal fetal males, have low circulating bio-LH levels compared with normal female controls at 80 days of gestation (second trimester). In fetal males and PA females alike, such LH suppression may represent testosterone-mediated changes in hypothalamic regulation of LH secretion [62], altered either directly via androgen receptors [63,64] or indirectly via estrogen receptors, through target tissue aromatization of exogenous testosterone [65,66].…”