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.

Sexual dimorphic expression of ADH in rat liver: importance of the hypothalamic-pituitary-liver axis

2002 ◽  
Vol 283 (3) ◽  
pp. G646-G655 ◽  
Author(s):  
Francis R. Simon ◽  
John Fortune ◽  
Mieko Iwahashi ◽  
Eileen Sutherland
Keyword(s):  
Sex Steroids ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Gh Secretion ◽  
Male And Female Rats ◽  
Mrna Content ◽  
Hypophysectomized Rats ◽  
Adh Activity ◽  
Dimorphic Expression

Hepatic alcohol dehydrogenase (ADH) activity is higher in female than in male rats. Although sex steroids, thyroid, and growth hormone (GH) have been shown to regulate hepatic ADH, the mechanism(s) for sexual dimorphic expression is unclear. We tested the possibility that the GH secretory pattern determined differential expression of ADH. Gonadectomized and hypophysectomized male and female rats were examined. Hepatic ADH activity was 2.1-fold greater in females. Because protein and mRNA content were also 1.7- and 2.4-fold greater, results indicated that activity differences were due to pretranslational mechanisms. Estradiol increased ADH selectively in males, and testosterone selectively decreased activity and mRNA levels in females. Effect of sex steroids on ADH was lost after hypophysectomy; infusion of GH in males increased ADH to basal female levels, supporting a role of the pituitary-liver axis. However, GH andl-thyroxine (T4) replacements alone in hypophysectomized rats did not restore dimorphic differences for either ADH activity or mRNA levels. On the other hand, T4 in combination with intermittent administration of GH reduced ADH activity and mRNA to basal male values, whereas T4 plus GH infusion replicated female levels. These results indicate that the intermittent male pattern of GH secretion combined with T4 is the principal determinant of low ADH activity in male liver.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Abstract 15602: Sex-differences in Extreme Exercise-induced Adverse Cardiovascular Remodeling

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gemma Sanguesa ◽  
Aline Meza ◽  
Anna Alcarraz ◽  
Cira Rubies ◽  
Lluis Mont ◽  
...  
Keyword(s):  
High Intensity ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Descending Aorta ◽  
Male And Female ◽  
Cardiovascular Remodeling ◽  
High Intensity Training ◽  
Male And Female Rats ◽  
Exercise Induced

Introduction: There is emerging evidence in men that sustained high-intensity training promotes an adverse cardiovascular remodeling, thereby increasing the risk of atrial fibrillation, ventricular arrhythmias and coronary calcification. Whether men and women are similarly affected by high intensity exercise-induced harm is unclear. Our aim was to study sex differences in a long-term endurance training rat model. Methods: Male and female Wistar rats were subjected to high intensity training for 16 weeks (INT, 60min 60cm/s, male n=20, female n=15). Sedentary rats (SED, male n=20, female n=18) were used as controls. At the end of the training period, rats had an electrocardiogram and echocardiography performed. Vascular fibrosis was assessed in descending aorta, left carotid, and intramyocardial arteries (IMA), right and left atria, and left ventricle (LV) histological samples. mRNA levels of cardiac hypertrophy, fibrosis, oxidative stress and inflammation genes were assessed in LV samples by Real-Time PCR. Results: INT male rats presented lower heart rate (382±9, 340±10, SED vs INT, p<0.01) and a longer QRS duration (18.8±0.6, 22.4±1.1, SED vs INT, p<0.01), while these were not modified in the INT female group. Echocardiography showed eccentric LV hypertrophy in both trained male and female rats. High intensity exercise induced fibrosis in the descending aorta and carotid in both males and females, but IMA were only affected in trained male rats. In the heart, exercise-induced atrial fibrosis similarly occurred in both trained male and female rats. No training-induced fibrosis was evident in the LV of both INT male and female rats. Regarding LV mRNA analysis, INT males showed a reduction of desmin, TTN and N2BA/N2B ratio, whereas INT females exhibited higher desmin mRNA levels and lower αMHC/βMHC ratio. Intense exercise did not increase LV mRNA levels of fibrosis, oxidative stress and inflammation markers neither in males nor in females. In comparison to males, females had lower LV myocardial fibrosis as well as lower fibrosis markers. Conclusions: Male and female rats exhibit qualitatively different cardiovascular remodeling after extreme exercise. Nevertheless, both sexes might develop exercise-induced adverse vascular and cardiac effects.

scholarly journals Leptin and glucocorticoid signaling pathways in the hypothalamus of female and male fructose-fed rats

2014 ◽  
Vol 66 (2) ◽  
pp. 829-839 ◽  
Author(s):  
Danijela Vojnovic-Milutinovic ◽  
Marina Nikolic ◽  
Jovana Dinic ◽  
Ana Djordjevic ◽  
Natasa Velickovic ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Leptin Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Leptin Sensitivity ◽  
Male And Female Rats ◽  
Glucocorticoid Signaling

Alterations in leptin and glucocorticoid signaling pathways in the hypothalamus of male and female rats subjected to a fructose-enriched diet were studied. The level of expression of the key components of the leptin signaling pathway (neuropeptide Y /NPY/ and suppressor of cytokine signaling 3 /SOCS3/), and the glucocorticoid signaling pathway (glucocorticoid receptor /GR/, 11?-hydroxysteroid dehydrogenase type 1 /11?HSD1/ and hexose-6-phosphate dehydrogenase /H6PDH/) did not differ between fructose-fed rats and control animals of both genders. However, in females, a fructose-enriched diet provoked increases in the adiposity index, plasma leptin and triglyceride concentrations, and displayed a tendency to decrease the leptin receptor (ObRb) protein and mRNA levels. In male rats, the fructose diet caused elevations in plasma non-esterified fatty acids and triglycerides, as well as in both plasma and hypothalamic leptin concentrations. Our results suggest that a fructose-enriched diet can induce hyperleptinemia in both female and male rats, but with a more pronounced effect on hypothalamic leptin sensitivity in females, probably contributing to the observed development of visceral adiposity.

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.

Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression

2003 ◽  
Vol 285 (6) ◽  
pp. E1273-E1281 ◽  
Author(s):  
Tatsuo Nakahara ◽  
Kijiro Hashimoto ◽  
Makoto Hirano ◽  
Michael Koll ◽  
Colin R. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Internal Standard ◽  
Alcohol Exposure ◽  
Female Rats ◽  
Male Rats ◽  
Skeletal Muscle Atrophy ◽  
Muscle Pathology ◽  
Mrna Levels ◽  
Male And Female Rats

Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6–7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (∼0.1–0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute effects of ethanol, indicative of a sensitization response; 5) the only effect seen with p53 mRNA levels was a decrease in muscle of rats starved for 1 day compared with fed rats, and there was no statistically significant effect on Bcl-2 mRNA in any of the experimental conditions. The increases in c-myc may well represent a preapoptotic effect, or even a nonspecific cellular stress response to alcohol and/or acetaldehyde. These data are important in our understanding of a common muscle pathology induced by alcohol.

Gonadal and sex steroid feedback regulation of gonadotrophin mRNA levels and secretion in neonatal male and female rats

1989 ◽  
Vol 3 (2) ◽  
pp. 139-144 ◽  
Author(s):  
P. Pakarinen ◽  
I. Huhtaniemi
Keyword(s):  
Sex Differences ◽  
Feedback Regulation ◽  
Female Rats ◽  
Male Rats ◽  
Sex Steroid ◽  
Mrna Levels ◽  
Negative Feedback Regulation ◽  
Α Subunit ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Serum and pituitary LH and FSH, and their pituitary mRNA levels, were measured in neonatal male and female rats after gonadectomy and after gonadectomy with sex steroid replacement. The animals were gonadectomized on day 3 of life, and those given sex steroid replacement were implanted with silicone elastomer capsules containing testosterone for males and diethylstilboestrol for females. Shamoperated rats served as controls. The animals were killed 4 or 8 days later and the sera and pituitaries collected. Pituitary contents of mRNAs for the α subunit, FSH-β and LH-β were determined by blot hybridization using corresponding cDNAs. Distinct sex differences were found in the mRNA responses to gonadectomy and steroid replacement. In the males, gonadectomy increased all mRNA levels at 7 days of age. In the females, a rise on day 7 was detected only for FSH-β; the other mRNAs were increased on day 11 of age. The steroid replacements reversed all the post-gonadectomy increases of mRNAs in both sexes. Moreover, the common α and LH-β mRNAs of the male animals were consistently suppressed below control levels. The serum concentrations of gonadotrophins increased after gonadectomy on day 7 in the males but only on day 11 in the females. The steroid replacements also suppressed the post-gonadectomy increases in serum gonadotrophins, but only the serum concentration of FSH in the females was reduced below controls. Pituitary gonadotrophin concentrations were not affected by gonadectomy, but the steroids suppressed LH in the males and FSH in the females. It is concluded that the onset of negative-feedback regulation of gonadotrophin synthesis by gonads and/or gonadal steroids starts earlier in male rats, before 7 days of age. In female rats these responses appear between 7 and 11 days of age. Clear sex differences were observed in how gonadotrophin mRNAs and pituitary and serum hormone levels responded to gonadectomy and steroid replacement in the neonatal period. Some of the responses differed from those previously reported in adult animals.

Effects of Sublethal Exposure to a Glyphosate-Based Herbicide Formulation on Metabolic Activities of Different Xenobiotic-Metabolizing Enzymes in Rats

2014 ◽  
Vol 33 (4) ◽  
pp. 307-318 ◽  
Author(s):  
Karen Larsen ◽  
Roberto Najle ◽  
Adrián Lifschitz ◽  
María L. Maté ◽  
Carlos Lanusse ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Liver Microsomes ◽  
Female Rats ◽  
Male Rats ◽  
Protective Mechanisms ◽  
Metabolizing Enzymes ◽  
Xenobiotic Metabolizing Enzymes ◽  
Male And Female Rats ◽  
Carbonyl Reduction ◽  
Metabolic Activities

The activities of different xenobiotic-metabolizing enzymes in liver subcellular fractions from Wistar rats exposed to a glyphosate (GLP)-based herbicide (Roundup full II) were evaluated in this work. Exposure to the herbicide triggered protective mechanisms against oxidative stress (increased glutathione peroxidase activity and total glutathione levels). Liver microsomes from both male and female rats exposed to the herbicide had lower (45%-54%, P < 0.01) hepatic cytochrome P450 (CYP) levels compared to their respective control animals. In female rats, the hepatic 7-ethoxycoumarin O-deethylase (a general CYP-dependent enzyme activity) was 57% higher ( P < 0.05) in herbicide-exposed compared to control animals. Conversely, this enzyme activity was 58% lower ( P < 0.05) in male rats receiving the herbicide. Lower ( P < 0.05) 7-ethoxyresorufin O-deethlyase (EROD, CYP1A1/2 dependent) and oleandomycin triacetate (TAO) N-demethylase (CYP3A dependent) enzyme activities were observed in liver microsomes from exposed male rats. Conversely, in females receiving the herbicide, EROD increased (123%-168%, P < 0.05), whereas TAO N-demethylase did not change. A higher (158%-179%, P < 0.01) benzyloxyresorufin O-debenzylase (a CYP2B-dependent enzyme activity) activity was only observed in herbicide-exposed female rats. In herbicide-exposed rats, the hepatic S-oxidation of methimazole (flavin monooxygenase dependent) was 49% to 62% lower ( P < 0.001), whereas the carbonyl reduction of menadione (a cytosolic carbonyl reductase-dependent activity) was higher ( P < 0.05). Exposure to the herbicide had no effects on enzymatic activities dependent on carboxylesterases, glutathione transferases, and uridinediphospho-glucuronosyltransferases. This research demonstrated certain biochemical modifications after exposure to a GLP-based herbicide. Such modifications may affect the metabolic fate of different endobiotic and xenobiotic substances. The pharmacotoxicological significance of these findings remains to be clarified.

The Influence of Sex Hormones on Rat Platelet Sensitivity to Adenosine-Diphosphate

1981 ◽  
Vol 46 (02) ◽  
pp. 496-499 ◽  
Author(s):  
M A Orchard ◽  
J H Botting
Keyword(s):  
Sex Hormones ◽  
Adenosine Diphosphate ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rat Platelets ◽  
Ovariectomised Rats

SummaryThe sensitivity of rat platelets to the aggregating agent adenosine-diphosphate (ADP) was studied. Platelets from male and female rats demonstrated comparable sensitivity. Neither ovariectomy nor castration altered platelet sensitivity to ADP. However platelets from mock-operated female, but not mockoperated male rats were less sensitive. Administration of physiological doses of l7β-oestradiol to ovariectomised rats reduced platelet sensitivity. Administration of l7β-oestradiol to mock operated female rats increased platelet sensitivity to ADP. The results suggest that physiological amounts of oestrogen induce a loss of platelet sensitivity following surgery or stress, whereas higher concentrations of oestrogens increase platelet sensitivity.

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