In females, it is well documented that progesterone (P) differentially affects specific limbic nuclei and related hypothalamic nuclei that regulate sociosexual behavior either by acting through genomic and/or non- genomic cellular mechanisms. However, for males there is limited knowledge on the functional and cellular aspects of this gonadal/ adrenal hormone. Prior research has shown that at pharmacological levels P possesses antiandrogenic properties that inhibit masculine reproductive behavior, but more recent studies in male rats and lizards have challenged the dogma that P attenuates reproductive behavior by antiandrogenic actions. These recent experiments have provided new evidence that at physiological levels P can actually facilitate aspects of copulatory behavior in gonadectomized males even in the absence of androgen replacement therapy. Furthermore, the P receptor antagonist RU486 reduces mating behavior in gonadally intact males, suggesting that P has a synergistic relationship with androgens that enhances reproductive behavior in males. The present studies will re-evaluate progesterone's role in the expression of male reproductive processes by neuroanatomically localizing the regions involved in P-mediated behavioral responses in males by intrahypothalamic microinjection of P (low levels) or RU486 (to block endogenous P receptors) in males primed with physiological levels of androgen. Subsequent studies will determine whether P-dependent behavioral responses are differentially regulated via genomic or non-genomic mechanisms by observing the rapid effect of microinjections (in select neuroanatomic sites) of P conjugated to bovine serum albumin (P-BSA). P-BSA does not diffuse freely through plasma membranes, binds specifically to plasma membranes, and triggers cellular responses to steroids within minutes. P's actions remain unclear in humans, yet, progestin therapy is used routinely as a means to control libido in felony sex offenders. The information derived from experiments in this proposal is fundamental to our understanding of the neurochemical pathways and cellular mechanisms underlying normal sociosexual behavior as well as deciphering pathological conditions associated with neuroendocrine dysfunction.
| Witt, D M; Gao, G; Caldwell, J D (2003) Testosterone and sexual experience alter levels of plasma membrane binding sites for progesterone in the male rat brain. Horm Metab Res 35:69-75 |
