R. S. Rosenfeld

Mild hypogonadotropic hypogonadism in obese men

To evaluate the pituitary-gonadal axis of obese men, we compared the 24-hour mean plasma concentrations of total and free testosterone and of dihydrotestosterone, FSH, and LH in 21 healthy obese men, aged 18-50, and 24 age-matched healthy nonobese men. In the obese men, we also measured the volume of ejaculate and the number and motility of sperm, and investigated libido by psychiatric interview, and potency by history and by measurement of nocturnal penile tumescence. As a group, the obese men had less than two-thirds the normal mean plasma levels of total testosterone, free testosterone, and FSH; the difference from normal was highly significant for all three. 24 hr LH levels were normal, which is inappropriately low in view of the subnormal testosterone levels. 24 hr mean levels of dihydrotestosterone and spermatogenesis, libido, and potency were essentially normal. Taken together, the findings represent a state of mild hypogonadotropic hypogonadism, which thus appears to be characteristic of obese men. This abnormality probably results from partial suppression of the pituitary by the elevated plasma estrogen levels we and others find in these men.

ISOTOPIC STUDIES OF PLASMA CHOLESTEROL OF ENDOGENOUS AND EXOGENOUS ORIGINS

This study was undertaken in order to compare the metabolic behavior of plasma cholesterol derived from the diet with that of cholesterol synthesized in vAvo from acetate (1). Cholesterol labeled with either isotopic carbon or hydrogen was administered orally to human subjects and the incorporation into plasma cholesterol was followed over an extended period. In certain instances, both endogenous and exogenous cholesterol metabolism were studied simultaneously by the use of appropriately labeled acetate and cholesterol. These techniques were also applied to an examination of the behavior of plasma cholesterol in four patients with hypercholesterolemia.

Reduction of Cholesterol and Lipids in Man by Ethyl p-Chlorophenoxyisobutyrate

Excerpt Thorp and Waring (1) studied a series of aryloxyisobutyric acids in rats for their ability to lower the level of cholesterol and lipids in serum and liver and found the compounds with maxim...

Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.

&NA; Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age‐matched men with typical Type B behavior pattern. Twenty‐four hour urine collections were divided into three periods: 9AM ‐ 6PM, 6PM to bedtime, and bedtime to 9AM. Type A men showed a significantly higher excretion than Type B men in the daytime (9AM ‐ 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.

Reduction of serum cholesterol and lipids by ethyl chlorophenoxyisobutyrate

Summary Oral administration of 2 g daily of ethyl-α-p-chlorophenoxyisobutyrate (CPIB) produces an excellent, sustained hypocholesterolemic and hypolipemic effect in man. The admixture of androsterone with CPIB was found to be unnecessary and failed to add anything to the effects of CPIB alone. Separate courses of treatment with CPIB alone and the combination of CPIB and androsterone were directly compared in 12 subjects and there was an almost identical decrease in serum cholesterol with either treatment. There was a striking sex difference in the hypocholesterolemic effect, women showing a much larger effect than men. Twenty-seven women treated with CPIB, alone or with added androsterone, showed an average 25 % decrease in serum cholesterol from 341 to 248mg/100ml, a 17% fall in serum phospholipids,and a 42% decline in serum triglycerides. Fourteen men similarly treated showed an average 12 % decrease in cholesterol; a 9 % fall in phospholipids; and a 30 % reduction of serum triglycerides. There was no evidence of any toxic effect on the liver, kidney, or bone marrow in this small series, and CPIB was well tolerated by all subjects. However, in subjects receiving coumadin, CPIB produced an augmentation of the anticoagulant effect which required reduction of the dose of coumadin. No bleeding tendencies or changes in prothrombin occurred in subjects not receiving coumadin. The mechanism of action of CPIB in reducing lipids is not known, but accumulation of desmosterol as a result of interference with the last steps of cholesterol synthesis has been excluded by the failure to detect desmosterol by vapor-phase chromatography. Since CPIB has been shown to produce an effective hypolipemic response without the occurrence thus far of side-effects, additional clinical trials are indicated to delineate its possible role in the prophylaxis and treatment of atherosclerosis.

THE RELATION OF PLASMA AND BILIARY CHOLESTEROL TO BILE ACID SYNTHESIS IN MAN

Bile is an important excretory route of steroids since it contains cholesterol and bile acids which are derived from cholesterol. That cholic acid is formed from cholesterol was demonstrated by Bloch, Berg and Rittenberg over a decade ago (1). Other workers have confirmed this finding in animals (2-6) and the conversion has also been demonstrated in the human (7, 8). Intermediates involved in this transformation have been extensively studied and reviewed by Bergstrom and Borgstrom (9, 10) and these workers have more recently reported on the stereochemical course of the transformation of cholesterol to cholic acid (11). This investigation deals with the dynamic aspects of the conversion of cholesterol of both endogenous and exogenous origins to cholic acid in man. Cholesterol-4-C14 and sodium acetate-H3 were fed to one subject, and sodium acetate-2-C14 was administered to a second subject; both had complete bile fistulas. It was found that orally in-gested cholesterol and biosynthetic cholesterol mixed indistinguishably in the plasma after a short equilibration period. Plasma and biliary cholesterol had the same specific acivity and were in isotope equilibrium with the pool which served as the precuirsor of cholic acid. EXPERIMENTAL Clinical material. The subjects were hospitalized on a metabolic ward where complete collections of urine, feces and bile could be made. Subject A was a 58 year old white man who had an external bile fistula established surgically for the relief of a bile duct obstruction due to

Excretion of steroid acids in man.

Abstract A procedure for the isolation of acids from defatted ethanolic extracts of human feces has been described which involves chromatography of their crude methyl ester acetates on silica gel. 10-Hydroxystearic acid, lithocholic acid, and deoxycholic acid have been shown to be the principal constituents of the alcohol-soluble acid fraction. It has been shown that the specific activity of deoxycholic acid in the feces is approximately equal to that of plasma ester cholesterol by the ninth day after the administration of cholesterol-4-C 14 to patients. A method has been presented which permits calculation of the fecal excretion of bile acids after the administration of a tracer dose of cholesterol-4-C 14 . This requires measurement of the total radioactivity in the stool acid fraction and determination of the specific activity of plasma cholesterol; by this method, an average excretion of 290 mg./day of bile acids has been found for the patients studied.

Direct analysis of dehydroisoandrosterone in plasma

DHA (1) has been measured in plasma by a radioimmunoassay procedure using an antiserum to DHA-7-BSA whose specificity is such that the procedure is carried out directly on diluted, unextracted plasma. The method has been used to obtain plasma DHA secretory patterns and mean concentrations and the data are in accord with those determined by related but more laborious techniques.

Radioimmunoassay of androsterone and androsterone-3-sulfate in plasma

Details of a sensitive and specific radioimmunoassay for androsterone (1) and androsterone sulfate in plasma have been presented. Benzene extracts of plasma were chromatographed on alumina to isolate the androsterone fraction either (a) directly after extraction (A) or (b) after solvolysis (AS). Following treatment with rabbit anti-A-17-BSA, antibody bound steriod was precipitated by ammonium sulfate. Androsterone concentrations in normal male plasma averaged 57 +/- 24 (S.D.) ng/dl, range 35-135 ng/dl and for normal women, 44 +/- 21 (S.D.) ng/dl, range 18-98 ng/dl. Androsterone sulfate concentrations were: males 55 +/- 28 mug/dl (range 10-114 mug/dl); premenopausal females 52+/- 31 mug/dl (range 16-318 mug/dl).

Measurement of solvolyzable esters of androsterone and dehydroisoandrosterone in human plasma

Abstract A method has been presented for the determination of the solvolyzable esters of androsterone and dehydroisoandrosterone in human plasma. The procedure involves the addition of tracer amounts of [4-14C] dehydroisoandrosterone and [3-3H] androsterone to plasma after extraction of the free steroids followed by protein precipitation, solvolysis, defatting, alumina chromatography, and thin layer chromatography. Quantitation is done by gas-liquid chromatography of the trimethylsilyl ethers. Replicate analyses of two large pools of adult human plasma gave values of 38 ± 2 μg and 47 ± 3 μg for androsterone and 147 ± 16 μg and 152 ± 10 μg for dehydroisoandrosterone as solvolyzable esters. Levels in 31 females and 24 males are reported. The procedure is applicable for routine laboratory use.