Response : Neuroendocrine Response to Estrogen and Sexual Orientation

Abstract

marmosets (4), estradiol stimulated similar increments in serum LH concentrations in both males and females, provided the animals were gonadectomized at the time estrogen was given. No such estrogen-induced surge in LH was seen in male macaques with gonads (5). Daily intramuscular injections of 1.5 mg of estradiol benzoate (EB) into four castrated men of unspecified sexual orientation caused a significant depression in serum LH, followed by a significant surge in LH secretion 120 hours after the onset of treatment (6). This EB-induced stimulation of LH secretion resembled the effects of estrogen in women with gonads (7). Daily EB injections caused smaller, but statistically significant, increases in serum LH within 96 hours in men with gonads (n = 6, sexual orientation not specified) (6). These findings strongly suggest that in male primates (heterosexual men included) the neuroendocrine mechanism mediating positive feedback effects of estrogen on LH secretion is not appreciably "defeminized" during sexual differentiation.The reported inability of estrogen to facilitate LH secretion in males with gonads in some primate species has been attributed to the potent inhibitory action of a testicular hormone on the responsiveness of the neuroendocrine axis to estrogen (8). The identity of this testicular factor is not known, although evidence from male macaques (8) suggests that it is neither testosterone nor dihydrotestosterone. It is possible that the heightened concentrations of LH observed by Gladue et al. (1) Psychoendocrine studies in humans are rarely singularly definitive and allconclusive, particularly in such a complex research area as behavioral psychobiology involving the hypothalamic-pituitary-gonadal axis. In our report (1) the main objective was to experimentally evaluate earlier suggestions by Dorner and his colleagues that a neuroendocrine response difference might exist related to differences in sexual orientation. It was those earlier reports that suggested adult LH response differences might reflect subtle differences in prenatal sexual differentiation and that those developmental influences were on the central nervous system. We found a differential response pattern in LH among the homosexual men that suggests a neuroendocrine responsiveness between that of the heterosexual men and the heterosexual women. We also discovered that some testicular differences might exist because testosterone concentrations also differed when estrogen was administered. We noted that those findings invite "the idea that there may be physiological developmental components in the sexual orientation of some homosexual men" and that "even though a developmental relation between neuroendocrine response and sexual orientation is not certain, our findings are not inconsistent with suck an interpretation" (1). Our objective then, and now, is to understand those physiological components that may be involved in psychosexual development.However, there can be alternative explanations and interpretations of these data, as we cauti...

Neurohormonal functioning and sexual orientation: A theory of homosexuality–heterosexuality.

“…Following evidence of an F/dM pattern of LH surges in response to estradiol injections among many male rats who had had their sexual orientations experi-mentally inverted (Dorner, 1967(Dorner, , 1972Kalcheim et ah, 1981), Dorner, Rohde, Stahl, Krell, and Masuis (1975) reported similar tendencies in about one-half of a group of human male homosexuals. More recently, Gladue, Green, and Hellman (1984) also found that about one-half of the male homosexuals they tested exhibited an LH surge in response to estradiol injections, something that was found in almost no male heterosexuals.…”

Plasticity in Brain Sexuality Is Revealed by the Rapid Actions of Steroid Hormones

“…Therefore, we propose that the fundamental organization/activation theory of steroid hormone action, [that steroids bind to nuclear receptors during development and adulthood to shape neural/behavioral phenotypes (Phoenix et al, 1959;Arnold and Breedlove, 1985;Emerson, 2000)], can be expanded to include the rapid actions of steroid hormones on the neurophysiological mechanisms of adult behavior. Comparable steroid mechanisms may explain the widespread distribution of divergent neural/behavioral patterns among teleosts with ARTs, as well as the many examples of intrasexual divergence in behavioral phenotypes among tetrapods (Rhen and Crews, 2002;Roselli et al, 2004), including humans and other primates (Gladue et al, 1984;Maggioncalda et al, 2002;Morris et al, 2004). The androgen receptor antagonist CA eliminates the rapid effects of androgens in type I and type II males, but not females, whereas the aromatase inhibitor FAD blocks the rapid effects of androgens in females but not type I and type II males.…”

Central pattern generators for social vocalization: Androgen-dependent neurophysiological mechanisms

“…This perspective may have important implications for the atypical neuroendocrine phenotypes associated with intrasexual divergence in social behavior among tetrapods (Rhen and Crews 2002;Roselli et al, 2004), including humans and other primates (Gladue et al, 1984;Maggioncalda et al, 2002;Morris et al, 2004). Divergent androgen mechanisms on CPGs may be particularly important, since the rapid actions of 11kT and testosterone appear to be highly steroid-specific in midshipman (Remage-Healey and Bass, 2007).…”