Neuroendocrine regulation of sexually dimorphic brain structure and associated sexual behavior in male rats is genetically controlled

Steroid hormones, particularly 17 beta -estradiol (E-2), regulate the devel opment and expression of neural structures and sexual behavior. Recently, w e demonstrated that E-2-regulated responses are controlled by quantitative trait loci. In this study, we quantified 1) volume of the sexually dimorphi c nucleus (SDN) of the preoptic area (POA); 2) medial basal hypothalamic (M BH)-POA aromatase and 5 alpha -reductase enzyme activities during prenatal development and in adults; 3) serum LH, testosterone, FSH, E-2, prolactin ( PRL), and corticosterone levels; 4) reproductive organ (i.e., testis and ve ntral prostate) weights; and 5) male mating behavior in Noble (NB/Cr) and W istar-Furth (WF/NCr) rat strains to determine the genetic influence on the measured parameters. Maximal phenotypic divergence in male SDN-POA volumes was seen between NB/Cr versus WF/NCr and BDIX/Cr rats (among nine rat strai ns initially examined), with the average SDN-POA volume of NB/Cr male rats being significantly greater (approximate to 30%) than that of either WF/NCr or BDIX/Cr males. Subsequent experiments investigated WF/NCr versus NB/Cr male rats in further detail. Significantly higher MBH-POA aromatase activit y was seen in adult WF/NCr versus NB/Cr males, while MBH-POA 5 alpha -reduc tase rates were not significantly different (within or between sex) for the two rat strains assayed. Serum LH levels were significantly higher (by gre ater than sixfold) in WF/NCr versus NB/Cr males, whereas testis organ:body weight and ventral prostate:body weight ratios in WF/NCr versus NB/Cr males were significantly smaller (by approximate to6-fold for testis and approxi mate to1.5-fold for prostate values). Serum FSH levels were significantly h igher (by twofold) in WF/NCr versus NB/Cr males. However, serum testosteron e levels were not significantly different, whereas E-2 levels were approxim ately twofold higher (but not significantly different) in WF/NCr versus NB/ Cr animals. No significant differences were found in basal (i.e., nonstress ) serum PRL or corticosterone levels between the WF/NCr and NB/Cr males. In male copulatory tests, NB/Cr males exhibited significantly more aggressive sexual behavior (e.g., in mounting, intromission, and ejaculation paramete rs) compared with WF/NCr males. Taken together, these findings indicate tha t WF/NCr males are, in general, low responders, whereas NB/Cr males are hig h responders to hormonal signals. The obtained data suggest that the correl ative, phenotypic variation in SDN-POA volume (i.e., structure) and reprodu ctive hormone patterns and mating behavior (i.e., function) of WF/NCr versu s NB/Cr males is regulated by potentially E-2-mediated mechanisms that are genetically controlled.