Androgen Imprinting of the Brain in Animal Models and Humans With Intersex Disorders: Review and Recommendations

The present report demonstrates the existence of a marked sexual difference in the volume of an intensely staining cellular component of the medial preoptic nucleus (MPON) of the rat. Moreover, this sexual dimorphism is shown to be independent of several specific hormonal conditions in the adult, but significantly influenced, perhaps determined, by the perinatal hormone environment. Adult rats were gonadectomized and sacrificed 2 or 5-6 weeks later, or sacrificed after gonadectomy and priming with estradiol benzoate (2 microgram/day x 3) and 500 microgram progesterone, or testosterone propionate (TP, 500 microgram/day x 14), or the ingestion of propylthiouracil (0.15% of the diet) for one month, or following water deprivation for 24 h. These treatments did not affect the sexual dimorphism in the MPON and, in all groups, nuclear volume in the male animals was significantly greater than that of females whether nuclear volume was expressed in absolute terms or relative to brain weight. On the other hand, the volume of the MPON of the adult male castrated neonatally was significantly reduced when compared to that of the male castrated at the time of weaning, i.e. after the period of sexual differentiation of the brain. Consistent with the view that this nuclear region undergoes sexual differentiation is the fact that the volume of the MPON was significantly greater in female rats injected with 1 mg TP on day 4 of life than in oil-treated females. More subtle sex differences in the volume of the suprachiasmatic nucleus were also detected, as were several treatment effects. Although these differences may fall within the error of the analytical procedure, it is possible that hormone- or sex-dependent morphological differences exist elsewhere in the brain. Nevertheless, the gross sexual dimorphism in the MPON clearly demonstrates a possible morphological basis for the sexual differentiation of brain function.