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

Saez, J.M.; Forest, Maguelone G.; Morera, A.M.; Bertrand, J

doi:10.1172/jci106917

Cited by 90 publications

(38 citation statements)

References 30 publications

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“…hAMH serum concentration was assayed by an ELISA (15), which does not recognize the mouse hormone. Testosterone and dihydrotestosterone (DHT) were assayed by specific RIA as described (16,17). Serum luteinizing hormone (LH) was measured by an immunofluorometric assay (18), and FSH measurements were done with the National Institutes of Health rat FSH RIA kit according to the instructions of the supplier.…”

Section: Methodsmentioning

confidence: 99%

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

Racine

Rey

Forest

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

230

143

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Strong overexpression of anti-Müllerian hormone (AMH) in transgenic mice leads to incomplete fetal virilization and decreased serum testosterone in the adult. Conversely, AMH-deficient mice exhibit Leydig cell hyperplasia. To probe the mechanism of action of AMH on Leydig cell steroidogenesis, we have studied the expression of mRNA for steroidogenic proteins in vivo and in vitro and performed a morphometric analysis of testicular tissue in mice overexpressing the hormone. We show that overexpression of AMH in male transgenic mice blocks the differentiation of Leydig cell precursors. Expression of steroidogenic protein mRNAs, mainly cytochrome P450 17␣-hydroxylase͞C17-20 lyase (P450c17), is decreased in transgenic mice overexpressing AMH and in AMH-treated purified Leydig cells. In contrast, transgenic mice in whom the AMH locus has been disrupted show increased expression of P450c17. In vitro, but not in vivo, AMH also decreases the expression of the luteinizing hormone receptor. The effect of AMH is explained by the presence of its receptor on Leydig cells. Our results provide insight into the action of AMH as a negative modulator of Leydig cell differentiation and function.

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Section: Methodsmentioning

confidence: 99%

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

Racine

Rey

Forest

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

230

143

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“…In the late 1960 s and the 1970 s, several papers were published giving MCRs for sex steroids and some of their metabolites in adult men and women (7)(8)(9)(10)(11)(12). MCRs have been published for testosterone in prepubertal children with congenital adrenal hyperplasia (13) and in two prepubertal individuals with androgen resistance (11). However, in both these conditions the endogenous hormone milieu is highly abnormal due to the disease state and the MCRs obtained in these prepubertal patients cannot be considered to reflect MCRs in healthy prepubertal children.…”

Section: Endogenous Production Of Sex Steroids In Humans Especially mentioning

confidence: 99%

“…The papers that the report refers to regarding the PR of estradiol (14) and progesterone (15) in prepubertal boys, and the PR of testosterone in prepubertal girls (11,13) do not give any information on the MCRs or PRs in healthy prepubertal children. They do, however, give information on the plasma concentrations of these hormones in children.…”

Section: Endogenous Production Of Sex Steroids In Humans Especially mentioning

confidence: 99%

Exposure to exogenous estrogens in food: possible impact on human development and health

1999

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There has been increasing concern about the impact of environmental compounds with hormone-like action on human development and reproductive health over the past decades. An alternative but neglected source of hormone action that may be considered in this connection is hormone residues in meat from husbandry animals treated with sex steroid hormones for growth promotion. Treatment of cattle with naturally occurring or synthetic sex hormones may enhance lean muscle growth and improve feed efficiency and is therefore a very cost effective procedure for cattle producers who have used it for decades in some Western countries, including the USA and Canada. The Joint Food and Agricultural Organisation/World Health Organisation (FAO/WHO) expert committee on food additives (JECFA) and the US Food and Drug Administration (FDA) considered, in 1988, that the residues found in meat from treated animals were safe for the consumers.We have re-evaluated the JECFA conclusions regarding the safety of estradiol residues in meat in the light of recent scientific data, with special emphasis on estradiol levels in prepubertal children. These levels are needed for estimates of the normal daily production rates of estradiol in children, who may be particularly sensitive to low levels of estradiol.In our opinion, the conclusions by JECFA concerning the safety of hormone residues in meat seem to be based on uncertain assumptions and inadequate scientific data. Our concerns can be summarized as follows. 1) The data on residue levels in meat were based on studies performed in the 1970 s and 1980 s using radioimmunoassay (RIA) methods available at the time. The sensitivity of the methods was generally inadequate to measure precisely the low levels found in animal tissues, and considerable variation between different RIA methods for measuring steroids exists. Therefore the reported residue levels may be subject to considerable uncertainty. 2) Only limited information on the levels of the various metabolites of the steroids was given despite the fact that metabolites also may have biological activity. 3) Reliable data on daily production rates of steroid hormones were and are still lacking in healthy prepubertal children. This lack is crucial as previous guidelines regarding acceptable levels of steroid residues in edible animal tissues have been based on very questionable estimates of production rates in children. Thus, even today the US FDA bases its guidelines on the presumably highly overestimated production rates in prepubertal children given in the JECFA 1988 report. 4) The possible biological significance of very low levels of estradiol is neglected.In conclusion, based on our current knowledge possible adverse effects on human health by consumption of meat from hormone-treated animals cannot be excluded.

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“…an interaction with their specific nuclear receptors) and metabolism [16]. A well-documented consequence of SHBG binding is its influence on the metabolic clearance rate of testosterone [17], Because SHBG level is lower in males than in females, the metabolic clearance rate of tes tosterone is faster in males than in females [17], and decreases in relation to the rise of SHBG levels during pregnancy and in hyperthyroidism [18].…”

Section: 14 15]mentioning

confidence: 99%

Clinical Utility of Sex Hormone-Binding Globulin Measurement

Pugeat¹,

Crave²,

Tourniaire³

et al. 1996

Horm Res

106

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The high-affinity binding of the sex hormone-binding globulin (SHBG) for testosterone and to a lesser extent for estradiol influences the circulating levels of these sex steroid hormones, their biodisposal to target cells as well as their mutual balance. Although the regulation of SHBG is still not completely understood, in vitro studies performed with human hepatocarcinoma (Hep G2) cells have shown that estrogens and thyroxine stimulate SHBG secretion, by increasing the steady state of its mRNA concentrations. These observations are in good agreement with studies showing that SHBG levels increase during oral administration of estrogens as well as in patients with thyrotoxicosis. Interestingly, SHBG levels are normal in syndromes such as the abnormal transport of thyroid hormones and/or the syndrome of thyroid hormone resistance, which can be confused with thyrotoxicosis. By constrast, the effects of androgens are controversial. In many patients with hirsutism, SHBG concentrations are low and correlate negatively with both body mass index and fasting insulin levels. Because of the inhibitory effect of both insulin and insulinlike growth factor-1 on SHBG secretion by Hep G2 cells in vitro, it has been proposed that SHBG levels could be a marker of insulin resistance and/or hyperinsulinism in humans. Furthermore, an increased risk for either noninsulin-dependent diabetes and/or the overall mortality are associated with decreased SHBG levels in postmenopausal women. Finally, in men, SHBG levels are positively correlated with the concentration of high-density lipoprotein cholesterol. Therefore, the measurement of SHBG in clinical practice can be a useful diagnostic tool for: (1) correctly interpretating testosterone and estradiol serum concentrations; (2) investigating androgen-estrogen balance in gonadal and sexual dysfunctions; (3) assessing the peripheral effect of the hormones which regulate SHBG productions, and (4) evaluating insulin resistance and cardiovascular risk.

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

Cited by 90 publications

References 30 publications

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

Exposure to exogenous estrogens in food: possible impact on human development and health

Clinical Utility of Sex Hormone-Binding Globulin Measurement

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