Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death.

The rat dentate gyrus undergoes a period of naturally occurring cell death during the first postnatal week. In the adult rat, removal of circulating adrenal steroids by adrenalectomy is followed by massive death in the granule cell layer, thus raising the possibility that developmental cell death results from low levels of these hormones. Interestingly, the first two postnatal weeks of life in the rat, termed the stress hyporesponsive period, are characterized by very low levels of adrenal steroids. In order to determine whether low levels of adrenal steroids enable developmental cell death to occur in the dentate gyrus, we examined the density of pyknotic and healthy cells in the dentate gyrus of rat pups which received one of the following treatments: (1) injections of the endogenous rat glucocorticoid corticosterone during the first postnatal week, or (2) adrenalectomy at the time when glucocorticoid levels normally rise. Quantitative analysis of the density of pyknotic cells in the granule cell layers revealed significant decreases with corticosterone treatment by the end of the first postnatal week. In these same brains, treatment with corticosterone resulted in a substantial increase in the density of pyknotic cells in the hilus. Adrenalectomy resulted in a significant increase in the density of pyknotic cells in the granule cell layer as well as in the hilus. Despite the dramatic alterations in the density of pyknotic cells with both increases and decreases in glucocorticoid levels, the density of healthy cells remained the same. These observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death.