DEVELOPMENTAL, DIURNAL AND OESTROUS CYCLE-DEPENDENT CHANGES IN THE ACTIVITY OF LIVER ENZYMES

1976 ◽  
Vol 68 (2) ◽  
pp. 265-272 ◽  
Author(s):  
ÅKE STENBERG
Keyword(s):  
Enzyme Activities ◽  
Reductase Activity ◽  
Maximal Activity ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Supernatant Fraction ◽  
Second Phase ◽  
Developmental Phase ◽  
Male And Female Rats

SUMMARY 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: 5β-reductase (supernatant fraction) and 5α-reductase, 17α- and 17β-hydroxysteroid reductases, 6β-, 7α- and 16α-hydroxylases (microsomal fraction). The activities of the 3α- and 3β-hydroxysteroid reductases were estimated by calculating the ratios of 3α-:5α- and 3β-: 5α-reduced metabolites formed, respectively. Most enzyme activities present at birth (i.e. 5β-reductase, 5α-reductase, 17β-hydroxysteroid reductase, 6β- and 7α-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 16α-hydroxylase and the 17α-hydroxysteroid reductase were induced, the 5β-reductase activity rapidly increased and the 5α-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 3β-hydroxysteroid reductase and a further increase in the activity of 16α-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16α-hydroxylase and the 17α-hydroxysteroid reductase activities disappeared, the 6β-hydroxylase and the 5β-reductase activities decreased and the 5α-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 16α-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5β-reductase activity reached a maximal activity during metoestrus.

PARTIAL FEMINIZATION OF HEPATIC STEROID METABOLISM IN MALE RATS AFTER NEONATAL ADMINISTRATION OF CYPROTERONE ACETATE

1975 ◽  
Vol 64 (2) ◽  
pp. 267-275 ◽  
Author(s):  
JAN-ÅKE GUSTAFSSON ◽  
MAGNUS INGELMAN-SUNDBERG ◽  
ÅKE STENBERG ◽  
FRIEDMUND NEUMANN
Keyword(s):  
Sexual Differentiation ◽  
Enzyme Activities ◽  
Cyproterone Acetate ◽  
Microsomal Fraction ◽  
Neonatal Period ◽  
Female Rats ◽  
Male Rats ◽  
Supernatant Fraction ◽  
Male And Female Rats ◽  
Neonatal Administration

SUMMARY The metabolism of [4-14C]4-androstene-3, 17-dione, [4-14C]5α-androstane-3α, 17β-diol and 1,2-3H]5α-androstane-3α, 17β-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of [4-14C]4-androstene-3, 17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changed in a direction characteristic of female rats: 5α-reductase active on 4-androstene-3, 17-dione increased in activity whereas 3β- and 17α-hydroxysteroid reductases and 6β- and 16α-hydroxylases active on 4-androstene-3, 17-dione and 2α-, 2β- and 18-hydroxylases active on 5α-androstane-3α, 17β-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3α- and 17β-hydroxysteroid reductases active on 4-androstene-3, 17-dione and 7α-hydroxylase active on both 4-androstene-3, 17-dione and 5α-androstane-3α, 17β-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rats were generally not affected although significant effects were noted in two cases; in one of these (17α-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with the anti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the present investigation may be used for more exact estimation of the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.

INDUCTION OF PROLACTIN AND LUTEINIZING HORMONE RELEASE BY HISTAMINE IN MALE AND FEMALE RATS AND THE INFLUENCE OF BRAIN TRANSMITTER ANTAGONISTS

1978 ◽  
Vol 76 (2) ◽  
pp. 193-202 ◽  
Author(s):  
A. O. DONOSO
Keyword(s):  
Prolactin Secretion ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Intraventricular Injection ◽  
Hormone Release ◽  
Stimulatory Action ◽  
Male And Female Rats ◽  
Oestradiol Benzoate ◽  
Lh Release

The levels of prolactin and LH in the plasma of rats were determined at various times after intraventricular injection of histamine. Doses of 5 and 60 μg histamine (free base) in male rats, anaesthetized with ether, induced an increase in the level of prolactin in the plasma, whilst producing a slight decrease in the concentration of LH. Injection of 5 μg histamine at 14.00 h into female rats at all stages of the oestrous cycle caused prolactin to be released; the effect was greatest at oestrus and at day 1 of dioestrus. Histamine also gave rise to a marked increase in the level of LH in the plasma when administered to pro-oestrous rats, but had no effect when injected at the other stages of the oestrous cycle. The effect of histamine on the release of prolactin in ovariectomized, oestradiol benzoate: progesterone-primed (OVX,OB:P) rats was found to be dose-related, and the level of LH in the plasma was increased by as little as 1·25 μg. Pretreatment with adrenergic (phenoxybenzamine and propranolol) and cholinergic (atropine) antagonists failed to block the stimulatory effects of histamine on prolactin secretion, but pretreatment with methysergide (serotonin antagonist) increased the histamine-induced release of prolactin in male rats. Antagonists did not modify the response of prolactin to histamine in OVX,OB:P-primed rats. The histamine-induced release of LH in OVX,OB:P-primed rats was slightly reduced by pretreatment with phenoxybenzamine, propranolol and atropine, but not by methysergide. These results indicate that histamine facilitates the release of prolactin. The stimulatory action of histamine on both pro-oestrous and OVX,OB:P-primed but not male rats suggests that histamine may be involved in LH release in the rat. Results obtained in animals pretreated with transmitter antagonists, which were unable to prevent histamine-induced hormone release, suggest that the actions of this amine are not mediated by cholinergic, noradrenergic or serotonergic mechanisms.

scholarly journals Androgen responsiveness of the liver of the developing rat

1974 ◽  
Vol 144 (2) ◽  
pp. 225-229 ◽  
Author(s):  
J-Å Gustafsson
Keyword(s):  
Testosterone Propionate ◽  
Neonatal Period ◽  
Female Rats ◽  
Male Rats ◽  
Second Phase ◽  
Final Phase ◽  
Male And Female ◽  
Androgen Treatment ◽  
Male And Female Rats ◽  
Developing Rat

The activities of the hepatic microsomal 2α-, 2β-, 7α- and 18-hydroxylase systems active on 5α-[4-14C]androstane-3α,17β-diol were studied in male and female rats which had been castrated at birth and at the age of 7, 13, 21, 27, 34, 43 and 55 days, treated for 5 days with 2mg of testosterone propionate/kg body weight and killed 6 days after castration. The 7α-hydroxylase system was affected very little by androgen treatment at all stages during development. On the other hand it was found that the rat liver passed through three phases during development with respect to androgen responsiveness as judged by changes in the activities of the 2α, 2β- and 18-hydroxylase systems: a first phase (from the neonatal period up to about 19 days of age) with a relative androgen unresponsiveness in both male and female rats, a second phase (from about 27 to about 33 days of age) when male and female rats responded equally well to androgens and a final phase (from about 40 days of age) with a successively decreasing androgen responsiveness in female rats but with a retained responsiveness in male rats. The hypothesis is presented that neonatal imprinting of the liver by testicular androgen(s) determines the development and degree of androgen responsiveness of liver tissue in the rat.

Rat adrenal 5α-reductase mRNA content and enzyme activity are sex hormone dependent

1991 ◽  
Vol 6 (2) ◽  
pp. 163-170 ◽  
Author(s):  
E. D. Lephart ◽  
E. R. Simpson ◽  
W. H. Trzeciak
Keyword(s):  
Enzyme Activity ◽  
Sex Hormones ◽  
Reductase Activity ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Immature Female ◽  
Male And Female Rats ◽  
Mrna Content ◽  
Reductase Mrna

ABSTRACT To investigate the effects of sex hormones on 5α-reductase, we examined 5α-reductase mRNA content and enzyme activity in the adrenal cortex of peripubertal male and female rats. In male rats, the influence of castration or hormone-replacement treatment with dihydrotestosterone (5α-DHT) on 5α-reductase was assessed. To stimulate ovarian sex hormone production in immature female rats, the effect of a single injection of 5 IU pregnant mare serum gonadotrophin (PMSG) on 5α-reductase was examined. The efficacy of the treatments was demonstrated by measuring serum LH and ventral prostate weight in male rats, and serum oestradiol and ovarian weight in female rats. Growth hormone was also measured across all treatments in male and female rats. Adrenal 5α-reductase mRNA levels were determined by RNA blot analysis utilizing a rat 5α-reductase cDNA as probe. 5α-Reductase enzyme activity was estimated by isolating [ 3H]5α-DHT by thin-layer chromatography after incubation with [3H]testosterone. The identity of the [3H]5α-DHT formed was demonstrated by recrystallization of the derivatized DHT to constant specific activity. In controls, adrenal cortical 5α-reductase mRNA content was nearly four times higher in immature female rats compared with intact peripubertal males. Castration resulted in a sevenfold increase in adrenal 5α-reductase mRNA content compared with that in intact controls, while in DHT-injected castrated animals the mRNA level was nearly undetectable. The content of adrenal 5α-reductase mRNA in anoestrous rats was nearly four times higher than in PMSG-treated animals. Adrenal 5α-reductase activity was higher in immature female rats than in intact peripubertal males. Castrated rats displayed more than a threefold increase in 5α-reductase activity over that of controls, whereas the activity values were below controls in castrated animals treated with DHT. In immature female rats treated with PMSG, 5α-reductase activity decreased by 40% to that of anoestrous controls. These results indicate that in the rat adrenal cortex the content of mRNA encoding 5α-reductase is negatively regulated by sex hormones presumably at the transcriptional level. Suppression of the enzymatic activity of adrenal 5α-reductase by sex hormones is due to lower mRNA levels encoding this protein.

CHANGES IN HYPOTHALAMIC PEPTIDASE ACTIVITY DURING THE OESTROUS CYCLE IN THE ADULT FEMALE RAT

1973 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper
Keyword(s):  
Enzyme Activity ◽  
Luteinizing Hormone ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Male Rats ◽  
Supernatant Fraction ◽  
Normal Male ◽  
Normal Female ◽  
Peptidase Activity ◽  
Female Rat

ABSTRACT The activity of peptidases in the rat hypothalamus which are capable of inactivating oxytocin has previously been found to vary with stimuli known to influence gonadotrophin release and may be related to both luteinizing hormone (LH) and luteinizing hormone releasing factor (LH-RF) release (Griffith & Hooper 1972a,b). In the present study, enzyme activity was determined in normal female rats during the morning and afternoon of each stage of the oestrous cycle, in normal rats, and in female rats injected neonatally with testosterone. The activity of the supernatant fraction was found to be not significantly different during the morning of each stage, but was greatly decreased on the afternoon of pro-oestrus; particulate activity did not vary during the oestrous cycle. Supernatant and particulate activities were found to be the same in normal male rats and testosterone-treated females, as previously shown. Both fractions' activities were significantly less than those found in the oestrous cycle, other than on the afternoon of pro-oestrus. These results indicate changes in hypothalamic peptidase activity during the oestrous cycle which may be inversely related to LH and LH-RF release; they also confirm the masculinizing effect of neonatal testosterone on the hypothalamus.

Sex-specific action of antiandrogens on androgen induced changes in hepatic microsomal 3β-hydroxysteroid dehydrogenase and 5α-reductase activity in the rat

1981 ◽  
Vol 98 (2) ◽  
pp. 261-266 ◽  
Author(s):  
E. Rodney Lax ◽  
Herbert Schriefers
Keyword(s):  
Enzyme Activities ◽  
Cyproterone Acetate ◽  
Reductase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Female Rats ◽  
Male Rats ◽  
Induced Changes ◽  
Intrinsic Effect ◽  
Gonadal Status ◽  
Antiandrogenic Activity

Abstract. The ability of two antiandrogens, cyproterone acetate and flutamide, to block the induction of microsomal 3β-hydroxysteroid dehydrogenase and repression of microsomal 5α-reductase in rat liver following administration of 5α-dihydrotestosterone was investigated in male and female castrated and female gonadintact rats. Although both antiandrogens blocked the effects of 5α-dihydrotestosterone on the seminal vesicles and uteri of gonadectomized rats at the doses employed, cyproterone acetate showed no antiandrogenic activity against the two enzyme activities. On the contrary when cyproterone acetate was administered alone it elicited a response similar to that seen after androgen administration; when given simultaneously with 5α-dihydrotestosterone, the induction of 3β-hydroxysteroid dehydrogenase activity was greater than after either steroid alone. In contrast the non-steroidal antiandrogen, flutamide, which had no intrinsic effect on either enzyme activity, effectively blocked 5α-dihydrotestosterone mediated changes in the enzyme activities of female rats regardless of gonadal status. However the influence of 5α-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.

INFLUENCE OF PROLACTIN ON THE METABOLISM OF STEROID HORMONES IN RAT LIVER AND ADRENALS

1975 ◽  
Vol 78 (3) ◽  
pp. 545-553 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Stenberg
Keyword(s):  
Microsomal Fraction ◽  
Testosterone Propionate ◽  
Reductase Activity ◽  
Hepatic Metabolism ◽  
Female Rats ◽  
Male Rats ◽  
Concomitant Treatment ◽  
Male And Female ◽  
Specific Effects ◽  
Male And Female Rats

ABSTRACT The influence of prolactin treatment on the hepatic metabolism of 4-[4-14C]androstene-3,17-dione (in the microsomal and 105 000 × g supernatant fractions) and 5α-[4-14C]androstane-3α,17β-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 5α-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 5α-reductase activity.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

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