The mode of action of steroid hormones: some recent findings.

Abstract

The author described results of the forward approach of studying the action of steroid hormones from their transport in blood to binding by target tissues uptake into the nucleus and possible mode of action on the synthetic machinery of the target cells. Steroids are found dissolved in plasma nonspecifically bound to plasma proteins and specifically bound to high affinity plasma proteins which exhibit however some overlapping recognition for steroids. Steroid hormones enter into target cells by protein-facilitated diffusion. Once incide some e.g. estradiol in rat uterus excert effects unchanged; others p articularly androgens are metabolized locally where the metabolites are more active than the original steroid prehormones. Very specific binding proteins have been isolated from the cytosol of all steroid hormone systems and they are known to be under physiological control in some systems e.g. estrogen and progestin receptors in guinea pig uterus. The steroid-receptor complex then migrates to the nucleus as shown by autoradiography and by cell-free systems. A nonhistone chromatin binding with virtually covalent binding affinity and another specific distinct from the cytosol-to-nucleus receptor have been implicated in steroid action. Current research is centering on the nature of early messenger-RNA and synthesis that initiates the response to steroid hormones. The author postulates early synthesis of a key intermediary protein (KIP). To support this idea he cites as evidence the IP or induced made in the first hour and susceptible to inhibition by actinomycin D and alpha-amanitin and a 15 S RNA fitting the description of mRNA. In general responses to steroid hormones are due to intracellular uptake of the steroid; perhaps modulated by but not necessarily requiring cyclic nucleotides PGs neurotransmitters or peptide hormones; probably entailing allosteric conformational changes in noncovalently bound specific receptors and positive feedback control at the transcriptional level.