Partial Masculinization of Rat Liver Enzyme Activities Following Treatment with FSH

Gustafsson, Jan‐Åke; Stenberg, Åke

doi:10.1210/endo-96-2-501

Cited by 24 publications

(5 citation statements)

References 4 publications

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“…None of the standards showed more than 15% of the potency of the female hypophyseal extract in increasing the activity of 5a-reductase when compared as activity per mg wet weight of pituitary tissue. This is in agreement with results found for the hepatic enzyme activities in the intact rat, as discussed above (6,7). The activity of the standards could possibly be due to contamination by the hypophyseal factor, which increases 5a-reductase activity, since none of the preparations used were entirely pure.…”

Section: Identification Of Metabolitessupporting

confidence: 91%

“…This control seems to be exerted via a hypophyseal "feminizing" factor, and most of the effects of estrogens and androgens on liver metabolism are probably mediated by changes in the secretion of this factor (5). Ex-periments where the effect of prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) on liver enzyme activities has been studied give no indication that these hormones are involved in the feminization of the hepatic enzyme pattern (6,7).…”

mentioning

confidence: 99%

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Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells.

Gustafsson

Larsson

Skett

et al. 1975

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

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A rat hepatoma cell line in tissue culture (HTC cells) was treated with hypophyseal extracts from adult male and female rats. Cell homogenates were then assayed for-steroid metabolizing enzymes using 4-androstene-3,17-dione as substrate. The major products were the 5a-reduced derivatives (5a-androstane-3,17-dione, androsterone, and epiandrosterone). When the cells were grown in the presence of female hypophyseal extract the apparent activity of the 5a-reductase increased markedly, whereas treatment with male hypophyseal extract was without effect. Treatment with female hypophyseal extract resulted in a marked decrease in the apparent Km for 5a-reductase from 667 & 120 to 99 + 4 jsM in addition to a decrease in the apparent Vmax from 67 i 12 to 46 + 2 pmol of product/min per mg of protein. A logarithmic dose-response was obtained with female hypophyseal extract. Treatment of the HTC cells with purified rat hypophyseal follicle-stimulating hormone, luteinizing hormone, growth hormone, thyrotropic hormone, and prolActin had only marginal effects on 5a-reductase activity. Crude female hypophyseal extracts were at least 6-fold more potent than any of the standard hormone preparations and at least 250-fold more potent than male hypophyseal extracts when based on activity per mg of pituitary tissue. Chromatography of crude female hypophyseal extracts on Sephadex G-25 indicated that the factor was of high molecular weight. The identity of this activity with a hypophyseal "feminizing" factor is postulated.Sexual differences in liver metabolism of steroid hormones in rats have been known for a long time (1-4). Recently, evidence has been presented that the sexual differentiation of liver steroid metabolism is controlled by the hypothalamicohypophyseal system (5). This control seems to be exerted via a hypophyseal "feminizing" factor, and most of the effects of estrogens and androgens on liver metabolism are probably mediated by changes in the secretion of this factor (5). Experiments where the effect of prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) on liver enzyme activities has been studied give no indication that these hormones are involved in the feminization of the hepatic enzyme pattern (6, 7).The regulation of hepatic steroid metabolism by the pituitary is important since it indicates the possible existence of a new hypophyseal hormone. The present paper describes the effect of a factor (or factors), present in the adult female rat pituitary, on tissue cultured hepatoma cells, which is similar to that of the "feminizing" factor on rat liver in vivo (5). The HTC cells thus seem to provide a potential tool for the isolation and characterization of such a factor. MATERIALS AND METHODS Steroids. 4-[4-14C]Androstene-3,17-dione was obtained from the Radiochemical Centre (Amersham, England) and purified by thin-layer chromatography. Unlabeled 4-androstene-3,17-dione, 3a-hydroxy-5a-androstan-17-one (androsterone), and 3,3-hydroxy-5a-androstan-17-one (epiandrosterone) were kindly donated...

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Section: Identification Of Metabolitessupporting

confidence: 91%

mentioning

confidence: 99%

Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells.

Gustafsson

Larsson

Skett

et al. 1975

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

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“…We also found that HCG reduced hexobarbitone hydroxylase activity in castrate males, although the depressive effects of the gonadotropin were twice as great when administered to intact mice. This extratesticular effect of HCG may be due to gonadotropic stimulation of adrenal androgen secretion (Blichert-Taft, Vejlsted, Kehlet & Albrechtsen, 1975), or possibly, gonadotropins can independently alter the levels of hepatic mono-oxygenases (Gustafsson & Stenberg, 1975). Nevertheless, our findings do suggest that the gonadotropin can reduce the activity of hepatic hexobarbitone hydroxylase by stimulating testicular secretion of androgens.…”

Section: Discussionmentioning

confidence: 60%

Androgenic repression of hexobarbitone metabolism and action in Crl:CD‐1 (ICR)BR mice

Shapiro

Szczotka

1984

British J Pharmacology

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“…The ectopic pituitary tissue is known to secrete prolactin and growth hormone and small amounts of the other anterior pituitary hormones (45)(46)(47)(48). In our experiments only prolactin and growth hormone could be measured in the serum of implanted animals (44 Gustafsson and Stenberg (49,50) have shown an effect of FSH but no effect of LH or prolactin on hepatic steroid metabolism when 4-androstene-3,17-dione is used as substrate. These results are in agreement with those of Colby et al (37), where corticosterone was used as substrate, and gain further confirmation from the April 1981 study of Lax et al (45), where the effect of prolactin on reductive metabolism was examined.…”

Section: Central Control Of Hepatic Steroid and Drug Metabolismmentioning

confidence: 69%

Role of the Hypothalamo-Pituitary-Liver Axis in Sex Differences in Susceptibility of the Liver to Toxic Agents

Gustafsson¹,

Eneroth²,

Hökfelt³

et al. 1981

Environmental Health Perspectives

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At birth testicular androgens irreversibly program brain centers involved in hypothalamopituitary control of hepatic sex-dependent steroid and drug metabolism. This imprinting process results in activation of a hypothalamic "feminostatin"-a secreting center that is turned on just before puberty. Feminostatin inhibits pituitary secretion of "feminizing factor," a pituitary hormone that feminizes the basal type of metabolism characterizing the liver of hypophysectomized and gonadectomized rats. Consequently, female rats that are devoid of feminostatin will secrete feminizing factor from the pituitary, leading to a feminine type of hepatic metabolism. Male rats have an active feminostatin-secreting center, and inhibition of pituitary feminizing factor release results in an autonomous type of liver metabolism. Female rats show a relative androgen unresponsiveness and seem incapable of releasing feminostatin after treatment with natural androgens, possibly because of more efficient metabolism (breakdown) of androgen in the female than in the male rat brain.Frontal deafferentation at the retrochiasmatic and suprachiasmatic level resulted in a complete "feminization" of hepatic steroid metabolism in male rats. Such an effect was also seen when lesions involving mainly the anterior periventricular hypothalamic area and the suprachiasmatic nucleus were performed in male rats. No effects were seen in analogous lesions in female rats in any of the cases studied. These findings suggest that a region including the anterior hypothalamic periventricular area, the suprachiasmatic nucleus and adjacent areas is involved in the control of hepatic steroid metabolism. It is postulated that the neuronal cell bodies that produce feminostatin have their origins in this area of the hypothalamus or may send axons through this area to the basal hypothalamus and thus directly or indirectly influence the anterior pituitary gland.Regulation by the central nervous system of a "lactogenic" (prolactin, Prl) receptor, present in the female rat liver, was also studied. This receptor is present in very low concentration or absent in the male rat. Anterior hypothalamic deafferentation at the retrochiasmatic level in male rats increased the hepatic Prl receptor concentration to the female level 3-4 days following the operation. A transection rostral to the suprachiasmatic nucleus had no effect on the concentration of Prl receptors in male animals. Our results demonstrate that the number of Prl receptors is regulated by the hypothalamo-pituitary system. The receptor-inducing pituitary factor might be related to the feminizing factor. Experiments were carried out to elucidate the nature of the Prl receptor-inducing pituitary factor. April 1981 129Human growth hormone (hGH) continuously administered was shown to induce Prl receptors in livers from male and female hypophysectomized-gonadectomized rats. The prolactin receptors were increased to a level found in control female rat livers. This inductive effect of hGH was also seen in adrenalectomized and...

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Partial Masculinization of Rat Liver Enzyme Activities Following Treatment with FSH

Cited by 24 publications

References 4 publications

Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells.

Influence of a novel hypophyseal factor on steroid metabolism in cultured hepatoma cells.

Androgenic repression of hexobarbitone metabolism and action in Crl:CD‐1 (ICR)BR mice

Role of the Hypothalamo-Pituitary-Liver Axis in Sex Differences in Susceptibility of the Liver to Toxic Agents

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