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Biomedical subjects

A Stenberg

Publications and source records attributed to A Stenberg.

At least 73 records · Page 4Linked to original sources

Metabolism of androstenedione in skin and serum levels of gonadotrophins and androgens in prepubertal boys with hypospadias.

The metabolism of 4-[1,2-3H]androstene-3,17-dione in the prepuce, axillary skin and skin from the arm was investigated in 27 boys operated for phimosis (controls) and 13 unselected boys with hypospadias (a congenital defect of the male urethra). In all types of skin investigated, androstenedione was metabolized to 5alpha-androstane-3,17-dione, 3alpha-hydroxy-5alpha-androstan-17-one, 3beta-hydroxy-5alpha-androstan-17-one and testosterone. Conversion to testosterone was found in the prepuce of two out of 11 boys with hypospadias. Mild forms of hypospadias in the age group 1--4 years had a higher level of 5alpha-reductase activity in the prepuce than controls in the same age group (P less than 0.05); no such differences were found in the few severe cases of hypospadias in this group. No other differences in 5alpha-reductase activity were found between hypospadic boys and controls. The ratio of 5alpha-reductase activity in the prepuce: 5alpha-reductase activity in skin from the arm was significantly higher (P less than 0.05) in hypospadic boys than in controls in the age group 1--4 years. Serum levels of LH and FSH were the same in normal and hypospadic boys but the concentration of prolactin in the serum was lower in boys with hypospadias compared with control subjects in the age group 1--4 years (P less than 0.005). No differences were found in serum concentrations of androstenedione, testosterone, oestradiol and testosterone-binding globulin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Specificity of neonatal, androgen-induced imprinting of hepatic steroid metabolism in rats.

The specificity of the neonatal, andreogen-induced, irreversible programming of hepatic steroid metabolism in the rat was investigated. 5-alpha-Dihydrotestosterone propionate and estradiol benzoate were as efficient as testosterone propionate in inducing a male type of liver metabolism in the adult animal, whereas epitestosterone propionate, etiocholanolone propionate, and o,p'-DDT were practically inactive in this respect. These findings indicate that different mechanisms are involved in neonatal imprinting of hepatic steroid metabolism and in the well-known neonatal androgenic and estrogenic induction of persistent estrus and acyclic gonadotropin secreqion.

Androgens↗

Feminization of hepatic S metabolism in male rats with a transplanted (MtT/F4).

After transplantation of MtT/F4 pituitary tumor cells to male rats of the Fisher strain, the masculine type of hepatic steroid metabolism was changed into a feminine pattern of enzyme activities. Liver metabolism of steroid hormones in female rats was relatively unaffected following transplantation of pituitary tumor cells. Futhermore, extract from MtT/F4 tumors and "autonomous" pituitary tissue increased the 5alpha-reductase activity of hepatoma cells in the culture (HTC cells) at subsaturation concentrations of the substrate 4-androstene-3, 17-dione by decreasing the apparent Km of the enzyme. It is concluded that the pituitary tumor (in accord with the secretion from an "autonomous" pituitary gland) secretes "feminotropin," a novel hypophyseal principle that probably is an important regulator of hepatic steriod metabolism. It is suggested that pituitary tumor tissue of the MtT/F4 type could be used as source of feminotropin in purification studies.

Androstenedione↗

On the obligatory role of the hypophysis in sexual differentiation hepatic metabolism in rats.

The hepatic metabolism of 4-[4-14C]androstene-3,17-dione and 5alpha-[4-14C]androstane-3alpha,17beta-diol was studies in castrated and hypophysectomized male rats with a transplanted pituitary under the kidney capsule. The effects of testosterone propionate and estradiol benzoate on liver metabolism were also studied in these experimental animals. It was found that the autonomous pituitary secreted a "feminizing factor" that transformed the male type of steroid metabolism characteristic of hypophysectomized rats into a female type of metabolism Hypophysectomized rats were unresponsive towards androgen action on the liver and did not respond with feminized hepatic metabolism after treatment with estradiol benzoate. It is concluded that estrogenic action on liver enzymes is mediated via modulation of the secretion of a central (probably hypothalamic) "feminizing factor inhibiting factor" and the sex hormonal effects of hepatic metabolism only occur in the presence of a pituitary in situ.

Androstane-3,17-diol↗

Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus.

The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally "feminized" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of "feminizing factor" from the female pituitary that is responsible for the "feminization" of the basically "masculine" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary "feminizing factor" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.

Androstane-3,17-diol↗

Developmental, diurnal and oestrous cycle-dependent changes in the activity of liver enzymes.

The metabolism of [4-14C]4-androstene-3, 17-dione was studied in the 105000 g microsomal and supernatant fractions of liver from developing rats of both sexes. The following enzyme activities were measured: 5beta-reductase (supernatant fraction) and 5alpha-reductase, 17alpha- and 17beta-hydroxysteroid reductases, 6beta-, 7alpha- and 16alpha-hydroxylases (microsomal fraction). The activities of the 3alpha- and 3beta-hydroxysteroid reductases were estimated by calculating the ratios of 3alpha-: 5alpha- and 3beta-: 5alpha-reduced metabolites formed, respectively. Most enzyme activities present at birth (i.e. 5beta-reductase, 5alpha-reductase, 17beta-hydroxysteroid reductase, 6beta- and 7alpha-hydroxylase) increased until 20 days of age in both male and female rats. Between 20 and 30 days of age a number of masculine metabolic characteristics appeared in both sexes, i.e. the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase were induced, the 5beta-reductase activity rapidly increased and the 5alpha-reductase activity slightly decreased. During a third period beginning 30 days after birth the adult male enzyme activity pattern was completed by the induction of 3beta-hydroxysteroid reductase and a further increase in the activity of 16alpha-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase activities disappeared, the 6beta-hydroxylase and the 5beta-reductase activities decreased and the 5alpha-reductase activity increased six times. The developmental patterns of enzyme activities in the rat liver are consistent with a first developmental phase (0-30 days of age) independent of hypophysial control and probably determined primarily by the genome of the liver cell and a second phase (from 30 days onwards) with increasing sexual differentiation under hypophysial control. This control is mediated by some kind of feminizing factor in female rats and possibly by some kind of androgen-elicited secretion of masculinizing factor(s) in male rats. The metabolism of [4-14C]4-androstene-3, 17-dione was also studied during different times of the day and during different phases of the oestrous cycle. The 16alpha-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5beta-reductase activity reached a maximal activity during metoestrus.

Age Factors↗

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

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-androsten-3,17-dione as substrate. The major products were the 5 alpha-reduced derivatives (5 alpha-androstane-3,17-dione, androsterone, and epiandrosterone). When the cells were grown in the presence of female hypophyseal extract the apparent activity of the 5 alpha-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 5 alpha-reductase from 667 +/- 102 to 99 +/- 4 muM in addition to a decrease in the apparent Vmax from 67 +/- 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 5 alpha-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.

Androstenedione↗

Partial masculinization of rat liver enzyme activities following treatment with FSH.

The metabolism of 4-(4014C)androstene-3,17-dione and 5alpha-(4-14C)androstene-3alpha, 17beta-diol was studies in the microsomal fraction and that of 4-(4-14C) androstene-3,17-dione in the 105,000 times g supernatant fraction of livers from castrated male and female rats treated with LH and FSH. Administration of LH led to significant decreases in 17-hydroxysteroid reduction and 7alpha-hydroxylation of 4-androstene-3,17-dione in both male and female rats and in 6beta-hydroxylation of 4-androstene-3,17-dione in female rats. FSH on the other hand specifically stimulated (masculinized) the following sex-dependent hydroxylations: 16alpha-hydroxylation of 4-androstene-3,17-dione in female rats and 2alpha-, and 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol in male rats. The metabolism of 4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol was also studied in castrated male and female rats given testosterone propionate and in castrated female rats given testosterone propionate in combination with LH or FSH. It was shown that neither LH nor FSH could compensate for the relative androgen-unresponsiveness exhibited by female as compared to male rats. It is concluded that FSH but not LH may participate in the regulation of sex-dependent hydroxylase systems in rat liver.?2,Author

17-Hydroxycorticosteroids↗

On the modulating effects of ovaries on neonatal androgen programming of rat liver enzymes.

The metabolism of 4-[4-14C]androstene-3,17-dione in rat liver microsomal and cytosol fractions was investigated in adult female rats treated with 1.45 mumole of testosterone propionate at birth. The effects of ovariectomy at 14 and 43 days of age on neonatal testosterone imprinting of enzyme levels were studied. Animals spayed 14 days after birth showed a typical masculinized hepatic enzyme activity pattern with a decreased level of the 5alpha-reductase activity and increased level of 5beta-reductase, 16alpha-hydroxylase and 17alpha- and 3beta-hydroxysteroid reductase levels. The pattern was essentially the same in testosterone propionate-treated rats spayed 43 days after birth - with the exception of a feminized 5alpha-reductase activity - whereas a completely feminized ("de-imprinted") pattern of enzyme activities was found in the rats with intact ovaries at the time of death. It is concluded that de-imprinting action of ovaries is mainly of a reversible nature.

Androstanes↗

Influence of prolactin on the metabolism of steroid hormones in rat liver and adrenals.

The influence of prolactin treatment on the hepatic metabolism of 4-(4-14C) androstene-3, 17-doine (in the microsomal and 105 000 times g supernatant fractions) and 5alpha-(4-14C) androstane-3alpha, 17beta-diol (in the microsomal fraction) and on the adrenal metabolism of 4-(4-14C) androstene-3, 17-dione was studied in intact and castrated male and female rats with and without concomitant treatment with testosterone propionate. Whereas prolactin gave a significant and specific decrease in the activity of adrenal 5alpha-reductase by about 20-30% in both male and female rats no specific effects were noted in the metabolism of steroids in the liver. Neither did prolactin compensate for the relative androgen unresponsiveness characteristic of neonatally castrated male rats. These results suggest that prolactin does not play any significant role in mediating the recently discovered hypophyseal control of sexual differentiation of hepatic steroid metabolism in the rat whereas it may have a function in maintaining sexual differences in alrenal 5alpha-reductase activity.

Adrenal Glands↗