Testosterone-Binding Levels in the Serum of Women During the Normal Menstrual Cycle, Pregnancy, and the Post-partum Period

A B S T R A C T The metabolic clearance rate (MCR) and blood production rate (BP) of testosterone (T) and dihydrotestosterone (DHT), the conversion of plasma testosterone to plasma dihydrotestosterone, and the renal clearance of androstenedione, testosterone, and dihydrotestosterone have been studied in man. In eight normal men, the MCRT (516±108 [SD] liters/m/day) was significantly greater than the MCRDIT (391±71 [SD] liters/m'/day). In seven females, the MCRT (304±53 [SD] liters/m'/day) was also greater than the MCRDET (209±45 [SD] liters/ m2/day) and both values were less than their respective values in men (P <0.001). In men the conversion of testosterone into dihydrotestosterone at 2.8±0.3% (SD) was greater than that found in females, 1.56±0.5% (SD) (P < 0.001). In five pregnant females the MCRT (192± 36 [SD] liters/m/day), the MCRDHT (89±30 [SD] liters/ m'/day) and the conversion of testosterone into dihydrotestosterone (0.72±0.15%) (SD) were significantly less than the values found in nonpregnant women. In five females with hyperthyroidism, the MCR for testosterone and dihydrotestosterone were similar to those observed in pregnant females, but the conversion of testosterone into dihydrotestosterone (2.78±1.7%) (SD) was greater, and similar to that found in men. In men the production of dihydrotestosterone was 0.39±0.1 (SD) mg/day, 50% being derived from the transformation of plasma testosterone. In women the production of DHT was 0.05± 0.028 (SD) mg/day, only 10% coming from testosterone. During pregnancy, the production of testosterone and dihydrotestosterone are similar to that in normal women. In three patients with testicular feminization syndrome A preliminary report of this work was presented at the 52nd Meeting of the Endocrine Society, June 1970.Received for publication 24 August 1971 and in revised form 20 December 1971. (an adult with hyperthyroidism and two children) these two MCRs were greatly reduced compared to the normal females, but the conversion of testosterone into dihydrotestosterone was in the limits of normal male rangeIn the normal subjects the renal clearance of androstenedione was greater than that of testosterone and dihydrotestosterone. Less than 20% of the dihydrotestosterone and less than 10% of the androstenedione in the urine is derived from the plasma dihydrotestosterone and androstenedione.

Section: Mcra Mcrt Mcrdht A-14c/t-14c T-$h/aand-sh Dht-14c/t-14c Dht-5hmentioning

confidence: 98%

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Saez¹,

Forest²,

Morera³

et al. 1972

“…Nevertheless, acute and chronic changes produced by testosterone could either be due to an increase in hepatic blood flow or to induction of enzymes involved in the metabolism of testosterone. Another explanation, however, could come from the studies of Pearlman and Crepy (24) who showed a significant binding of testosterone by human plasma, and that this binding capacity of plasma was dependent upon estrogen (25). Testosterone bound to plasma albumin can be considered as physiologically free testosterone since this binding is of low affinity (26).…”

Section: Conversion Ratios and [P] Values The Conversionmentioning

confidence: 99%

Metabolism of testosterone and androstenedione in normal and ovariectomized women

Abraham¹,

Lobotsky²,

Lloyd³

1969

A B S T R A C T Metabolic clearance rates of testosterone (MCRT) and androstenedione (MCRA) were determined twice during the same cycle in six normal women, using a constant infusion of testosterone-2H and androstenedione-"C. Nonlabeled steroids served as internal standards. Plasma concentrations of testosterone (iT) and androstenedione (iA) were measured, and the blood production of testosterone (PBT) and of androstenedione (PBA) were calculated. The interconversions of these two steroids were also estimated. Six ovariectomized women were studied in the same manner. For testosterone, the mean i in the normal women was not significantly different from that in the ovariectomized subjects, whereas the MCRT and PET were significantly lower in the ovariectomized subjects. For androstenedione, the mean MCRA values of the two groups of subjects were not different, whereas the iA and PBA in the normal women were about double those in the ovariectomized subjects. In comparing the follicular and luteal phases of the menstrual cycle in four of six subjects there was no difference in iT, MCRT, or PBT, whereas iA, MCRA, and PBA were increased in the luteal phase. In one ovariectomized woman infused with testosterone and androstenedione at physiologic levels, MCRT doubled but MCRA remained the same. After six wk on estrogen, the same subject did not show any change in MCRT after infusion of testosterone. It is suggested that MCRT depends on PBT and on plasma binding of testosterone which is partly estrogen dependent.

“…One can therefore wonder if the decrease in testosterone 5a-reduction observed in patients with feminizing testes reflects an enzymatic impairment or is only the result of the abnormal sensitivity of a specific enzyme to estrogens originating either directly from testes or indirectly from the peripheral conversion of testosterone and androstenedione (22,23). Estrogen may act by (a) inhibition of the enzyme allowing in target cells the hydrogenation of testosterone to androstanolone as the nuclear enzyme described by Bruchovsky and Wilson (12) or (b) increase of specific plasma protein binding testosterone (24,25) so that almost no unbound testosterone may be available in target cells for 5ca-reduction. This last hypothesis is sustained by the high binding levels for testosterone observed in the plasma of patients, and furthermore, seems very consistent regarding the hepatic 5P-reduction of testosterone which is very low when the steroid is injected intravenously but is normal when testosterone is orally administered.…”

Section: Introductionmentioning

confidence: 99%

Studies on testosterone metabolism in subjects with testicular feminization syndrome

Mauvais-Jarvis¹,

Bercovici²,

Crépy³

et al. 1970

115

A B S T R A C T The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17p-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5a-androstane-3a,17,-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5a-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5a-reduction of this substrate seems very unlikely.The metabolic abnormalities observed in patients with testicular feminization syndrome may be reproduced in normal males by estrogen treatment. Nevertheless, the sensitivity of the patients to estrogen seems to be 10 times greater than that of normal males. This sensitivity was appreciated from the reduction of radioactive testosterone intravenously injected to urinary 17P-hydroxy-5a-androstan-3-one and androstanediol and also from the level of plasma binding for testosterone. This level was significantly higher (P < 0.05) in patients with feminizing testes than in normal males. The level increased dramatically after administration of a low dose of estrogen whereas this effect was not observed in normal males under the same experimental conditions.In light of these results the defect of extrahepatic 5a-reduction of testosterone observed in patients with Part of this work has been published as a preliminary communication (14).