W. Roy Slaunwhite

Interaction of Prolactin and Testosterone in the Human Prostate

SummaryThree experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPr, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPr. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPr was measured and was found to be more than twice the uptake into tissue from those with low hPr (6.5±1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPr was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.

Conjugated and Unconjugated Plasma Androgens in Normal Children

Extract: Methods developed in this laboratory permit measurement of the androgens, testosterone (T), dehydroepiandrosterone (D), and androstenedione (Δ) on a 10-ml sample of plasma. We have determined concentrations of the unconjugated androgens (T, Δ, D) as well as of the sulfates of dehydroepiandrosterone (DS) and androsterone (AS) in the plasma of 85 healthy children of both sexes from birth through the age of 20 years. Our results are shown and summarized, along with those of other investigators.Testosterone was elevated in both sexes in the newborn as compared with the 1-8-year-old group. In contrast, sulfated androgens, with one exception, were undetectable early in life. In males, there was a marked rise in all androgens, especially T, in the 9-18-year-old group. The increase in plasma androgens occurred before clinical manifestations of increased androgens became evident. In females, there was only a modest increase in plasma androgens in the 9-18-year-old group except in the case of A which did not change. The greatest increases were in D, DS and AS. This is the first report of unconjugated androgen concentrations in the adolescent female.Speculation: Measurement of the plasma androgens will aid in evaluation of children with sexual infantilism or sexual precocity. The prepubertal rise in plasma testosterone in males may be accompanied by a higher level of plasma protein binding than that which is found after puberty becomes evident.

The Synthesis of 125I-2-Iodohistamine for Radioimmunoassay1

Recently radioactively labeled iodohistamines have been claimed to have superior shelf-life to the iodophenols more commonly used in radioimmunoassay of small molecules. This claim is based largely on theoretical considerations; no systematic study has appeared. We found that iodination of histamine on a macroscale proceeds rapidly at pH 7-8.4 to yield principally 2-iodohistamine. With a large excess of iodine, substantial diiodination can be achieved. In 0.5 N sodium hydroxide solution, triiodination produces 1,2,5-triiodohistamine; the N-I bond, however, is somewhat labile. 125I-2,5-Diiodohistamine is also somewhat unstable, having a first order decomposition rate of 1.6 X 10(-3) day-1 (t1/2, 182 days), while 125I-2-iodohistamine shows a barely perceptible change in 60 days (7.5 X 10(-5) day-1). The assignment of the first iodine introduced to C-2 is based on a comparison of the NMR spectra of monoiodohistamine and histamine. Iodination with carrier-free iodine-125 using the Hunter-Greenwood procedure (chloramine-T) produces a 76% yield of mono- and a 19% yield of diiodo product which are easily isolable by a single TLC using silica gel in the solvent system, ethanol:ethyl ether:water, 5:5:2.

Studies on phenolic steroids in human subjects: XIV. Studies on the fate of injected 6,7-H3-oestriol-3-C14-glucosiduronate

Labelled oestriol-3-glucosiduronate was administered to three human subjects in separate experiments: peripherally into a normal subject, peripherally into a subject with T-tube drainage, and peripherally with simultaneous instillation of 16-C14-oestriol into the portal vein of a third subject. n nResults show rapid excretion of the unchanged conjugate in the urine and no enterohepatic circulation. During this work, preliminary evidence is presented for the observation that in urine an equilibrium exists between oestriol-3-glucopyranosiduronic acid and its 3,6 lactone.