Prenatal administration of letrozole reduces SDN and SCN volume and cell number independent of partner preference in the male rat.

During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN). Interestingly, male rats perinatally treated with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), also showed bisexual preference and an increased number of vasopressinergic neurons in the SCN. However, this steroidal aromatase inhibitor has affinity for all three steroid receptors. Recently, we reported that the prenatal administration of the selective aromatase inhibitor, letrozole, produced a subpopulation of males with same-sex preference. The aim of this study was to compare the volume and number of cells of the SDN and SCN (the latter nucleus was immunohistochemically stained for vasopressin) between males treated with letrozole with same-sex preference, males treated with letrozole with female preference and control males with female preference. Results showed that all males prenatally treated with letrozole have a reduced volume and estimated cell number in the SDN and SCN, independent of their partner preference. These results indicate that the changes in these brain areas are not related to sexual preference, but rather to the effects of letrozole. The divergent results may be explained by species differences as well as by the critical windows during which the aromatase inhibitor was administered.

Reactivation of metabolically impaired neurons in Alzheimer’s disease

Several lines of evidence show that decreased metabolic rate precedes cognitive impairment in Alzheimer ’s disease (AD). Decreased neuronal metabolism contributes to neuronal atrophy and functional impairment and is thus an early occurring hallmark of AD. Factors that may contribute to a diminishment in neuronal metabolism are age, sex, APOE-ε 4 and decreased levels of sex hormones or melatonin. Several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon we paraphrased as “use it or lose it”. Moreover, a number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may to a certain degree restore several aspects of cognition and other central functions. For instance, the circadian system of Alzheimer patients may be restimulated by exposing them to more light or transcutaneous nerve stimulation. A procedure allowing testing of the efficacy of putative stimulatory compounds such as neurotrophins and precursor cells has been developed in order to be able to culture human postmortem brain tissue.

Sexual behavior reduces hypothalamic androgen receptor immunoreactivity.

Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express FOS-immunoreactivity in response to mating. In many species sexual satiation, a state of sexual behavior inhibition, is attained after multiple ejaculations. The mechanisms underlying sexual satiation are largely unknown. In this study we show that sexual activity reduces androgen receptor immunoreactivity (AR-ir) in some of the brain areas associated with the control of male sexual behavior, but not in others. Thus, one ejaculation reduced the AR-ir in the MPN and nAcc, but not in the BST and VMN. Copulation to satiation, on the other hand, reduced AR-ir in the MPN, nAcc and VMN, and not in the BST. The AR-ir reduction observed in the MPN of sexually satiated rats was drastic when compared to that of animals ejaculating once. Serum androgen levels did not vary after one ejaculation or copulation to exhaustion. These data reveal that sexual activity reduces AR in specific brain areas and suggest the possibility that such a reduction underlies the sexual inhibition that characterizes sexual satiety.