Age- and Sex-Dependent Biotransformation of Androgens in the Pituitary, Pineal Gland, and Arcuate Nucleus of the Hypothalamus of Rats

Abstract

Sex-steroid hormones are the principal mediators of feedback loops between reproductive and neuroendocrine organs. Hormone action on these structures may be accompanied by their biotransformation. Our present work is concerned with the investigation of androgen metabolism in the pituitary, pineal gland, and arcuate nucleus (AN) of the hypothalamus of rats. Isolated organs from male and female rats 5, 10, 15, 23, 30, 40, and 60 days old were incubated in 199 medium in the presence of 3H-androgens (concentration ∼ 10−8 M) : 4-androstene−3,17-dione, testosterone, 5α-androstane-17β-ol−3-one, 5a-androstane−3α, 17β−, and 3β, 17β− diols. Steroid metabolites were separated by TLC and their quantity were determined by radiometry. In all organs, biotransformation was found to be carried out by two principal steps: reduction of the steroids by Δ4-5α-steroid reductase, and reversible ketone-alcohol transformation by 3β- and 17β-hydroxysteroid oxido reductases. However, 5a-androstane-3 3, 17$-diol was transformed only into polar-unidentified compound. The differences in androgen metabolism in the organs of both sexes were found to be only of a qualitative nature: the most intensive biotransformation of all androgens was observed in the pineal gland: the lowest was in the AN of the hypothalamus. The intensity of metabolism was strongly dependent on the age of the rat: in the pineal gland, androgen transformation (with the exception of testosterone) increases to a maximum on the 10th day of life (for testosterone — on the 15th day) and sharply decreases up to the 23rd day. In the AN of the hypothalamus and the pituitary, maximal activity has been observed on the 5th day of life; it drops sharply until the 23rd day, and reaches minimal values at day 60. Extreme differences in the steroidogenesis are of several orders of magnitude. This suggests the existence of “critical periods” for androgen biotransformation in the neuroendocrine structures of the brain, which are probably connected with age and sexual differentiation.