Prednisolone modifies estrogen-induced sexual differentiation

It has been hypothesized that during the perinatal period androgen alters sexual development only after it is aromatized to estrogen intracellularly. The dose of estrogen needed to cause sexual differentiation, however, is larger than might be expected on the basis of the rate of estrogen production. This could be because estrogens are normally sequestered by plasma fetoneonatal estrogen-binding protein. To test this possibility neonatal female rats were administered a low dose of estrogen alone or in combination with the glucocorticoid prednisolone, a steroid that reduces blood levels of the estrogen-binding protein. The estrogen significantly inhibited adult lordotic behavior only when combined with the prednisolone, a treatment which had no effect by itself. The findings support the “aromatization hypothesis” and the suggestion that the fetoneonatal estrogen-binding protein protects the developing rat from differentiating effects of estrogen.