Effects of prenatal testosterone on sexual behavior, reproductive morphology and LH secretion in the female rat.

Sexual differentiation of many brain structures and functions is dependent on levels of testosterone (T) or its metabolites during certain 'sensitive' developmental periods. If T is present during these perinatal periods, masculinization and defeminization of sexual behavior occur; also, reproductive physiology, and central nervous system morphology and function are altered. The purpose of the present study was to characterize the influence of T at specific prenatal developmental intervals on offspring reproductive morphology, physiology, locomotor activity and sexual behavior during postnatal development. To avoid complications induced by endogenous testicular activity, only females were examined. Free T was used because of its relative short half-life, so that the effects induced by its administration on a specific gestational day (GD) could be evaluated. Pregnant rats received a single subcutaneous injection of either sesame oil (controls) or 5 mg of T on GD 16, 17, 18, 19, 20, 21, or 22. Female offspring of pregnant rats exposed to T displayed significant alterations in morphology and behavior. The anogenital distance, measured at 25 days postbirth, was significantly increased if T was administered on GD 16, 17 or 18. T treatment on GD 16 or each day thereafter through GD 20 significantly delayed the normal occurrence of vaginal opening (controls at 37.5 days vs. T treatment which ranged from 38.5 to 41.4 days). Abnormal vaginal morphology (enlarged clitoris) was also observed when T was injected during a similar prenatal interval (i.e. GD 16 to GD 22). Furthermore, prenatal T treatment on GD 18 (and each day thereafter), until GD 22 significantly decreased lordotic behavior compared to control values. However, exposure to T, on any prenatal GD did not alter the animals' ability to exhibit an induced luteinizing hormone (LH) surge. These results suggest that the onset for altered reproductive morphology occurs at least as early as GD 16, whereas the onset of sexual behavior sensitivity occurs precisely at GD 18, and that the normal pattern of adult LH release in females is not altered by prenatal androgen treatment using this specific paradigm.