Pike, John Wesley 1,25-dihydroxyvitamin D: Hormonal Regulation of Biosynthesis and Purification of Its Intestinal Receptor

The renal biosynthesis of 1,25-dihydroxyvitamin D (l,25-(OH)2B) is known to be stringently regulated by extensive ionic and hormonal controls. Quantitation of this mineral regulating hormone by radio­ receptor assay has recently enabled a study of its influence and syn­ thetic control during physiological states of growth and reproduction. The data reveal that 1,25-(0H)̂ D is strikingly elevated during those situations, most likely to mediate the enhanced absorption of mineral. Since the elevation of this sterol hormone dynamically coincides with the peak mineral demands of pregnancy and lactation, it suggests a rapid and precise modulation of 1,25-(OH)2D biosynthesis. Regulatory control of 1,25-(0H)2D apparently involves both pituitary and sex hormones. This is supported by the observation that hypophysectomy in growing rats leads to a dramatic fall in the sterol hormone, a depression reversed by growth hormone therapy. Further, estrogen (DES) or prolactin administration in chicks enhances circu­ lating 1,25-(0H)2D. Conversely, inhibition of prolactin secretion in lactating rats limits the synthesis of the sterol hormone. Although the inextricable relationship between l,25-(OH)2l' synthesis and para­ thyroid hormone is also demonstrated, the results lend strong support to other regulators of 1,25-(OH)2D biosynthesis. A primary target organ for 1,25-(OH)2D is the intestine, where the hormone is known to bind a specific cytoplasmic receptor prior to its effects on the enhancement of intestinal mineral absorption.