Regulation of 11β-hydroxysteroid dehydrogenase by sex steroids in vivo: further evidence for the existence of a second dehydrogenase in rat kidney

1993 ◽  
Vol 139 (1) ◽  
pp. 27-35 ◽  
Author(s):  
S. C. Low ◽  
S. N. Assaad ◽  
V. Rajan ◽  
K. E. Chapman ◽  
C. R. W. Edwards ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Mrna Expression ◽  
Sex Steroids ◽  
Rat Kidney ◽  
Indirect Evidence ◽  
Hydroxysteroid Dehydrogenase ◽  
Female Rats ◽  
Oestradiol Treatment ◽  
Male And Female Rats

ABSTRACT 11β-Hydroxysteroid dehydrogenase (11β-OHSD) catalyses the reversible conversion of corticosterone to inactive 11-dehydrocorticosterone, thus regulating glucocorticoid access to mineralocorticoid and perhaps glucocorticoid receptors in vivo. 11β-OHSD has been purified from rat liver and an encoding cDNA isolated from a liver library. However, several lines of indirect evidence suggest the existence of at least two isoforms of 11β-OHSD, one found predominantly in glucocorticoid receptor-rich tissues and the other restricted to aldosterone-selective mineralocorticoid target tissues and placenta. Here we have examined the effects of chronic (10 day) manipulations of sex-steroid levels on 11β-OHSD enzyme activity and mRNA expression in liver, kidney and hippocampus and present further evidence for the existence of a second 11β-OHSD isoform in kidney. Gonadectomized male and female rats were given testosterone, oestradiol or blank silicone elastomer capsules, controls were sham-operated. In male liver, gonadectomy+ oestradiol treatment led to a dramatic decrease in both 11β-OHSD activity (69 ± 8% decrease) and mRNA expression (97 ± 1% decrease). Gonadectomy and testosterone replacement had no effect on male liver 11β-OHSD. However, in female liver, where 11β-OHSD activity is approximately 50% of that in male liver, gonadectomy resulted in a marked increase in 11β-OHSD activity (120 ± 37% rise), which was reversed by oestradiol replacement but not testosterone treatment. In male kidney, gonadectomy+oestradiol treatment resulted in a marked increase in 11β-OHSD activity (103 ± 4% rise). By contrast, 11β-OHSD mRNA expression was almost completely repressed (99 ± 0·1% decrease) by oestradiol treatment. This effect of oestradiol was reflected in a loss of 11β-OHSD mRNA in all regions of the kidney showing high expression by in-situ hybridization. In female kidney, oestradiol replacement also led to an increase in 11β-OHSD activity (70 ± 15% rise) while mRNA expression fell by 95 ± 3%. None of the treatments had any effect on enzyme activity or mRNA expression in the hippocampus, although transcription starts from the same promoter as liver. We conclude that (i) sex steroids regulate 11β-OHSD enzyme activity and mRNA expression in a tissue-specific manner and (ii) the concurrence of increased enzyme activity with near absent 11β-OHSD mRNA expression in the kidney following oestradiol treatment suggests that an additional gene product is responsible, at least in part, for the high renal activity observed. Journal of Endocrinology (1993) 139, 27–35

THE INFLUENCE OF HAEMOGLOBIN-S AND G6PD DEFICIENCY ON THE ACTIVITY OF THE 17β-HYDROXYSTEROID DEHYDROGENASE OF INTACT HUMAN ERYTHROCYTES

1974 ◽  
Vol 75 (4) ◽  
pp. 793-800
Author(s):  
A. O. Sogbesan ◽  
O. A. Dada ◽  
B. Kwaku Adadevoh
Keyword(s):  
Enzyme Activity ◽  
Dehydrogenase Activity ◽  
Sex Steroids ◽  
G6pd Deficiency ◽  
Incubation Medium ◽  
Hydroxysteroid Dehydrogenase ◽  
G6pd Activity ◽  
Reverse Transformation ◽  
Oxidative Transformation ◽  
Haemoglobin S

ABSTRACT The 17β-hydroxysteroid dehydrogenase activity in intact erythrocytes of Nigerian patients, in particular with regard to haemoglobin genotypes and G6PD* activity was studied. The G6PD activity of the erythrocyte did not affect the oxidative transformation of testosterone to androstenedione and of oestradiol to oestrone. The reduction (reverse transformation) was inhibited in G6PD-deficient erythrocytes but this inhibition was offset by the addition of 0.025 m glucose to the incubation medium. The per cent oxidation transformation of testosterone was higher in Hb-AA than in Hb-SS erythrocytes. It is suggested that the differences may be a result of either lower enzyme activity in the Hb-SS erythrocytes or of differences in the uptake and possibly binding of sex steroids by intact Hb-SS and Hb-AA erythrocytes.

11 beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon

1993 ◽  
Vol 264 (6) ◽  
pp. E951-E957 ◽  
Author(s):  
C. B. Whorwood ◽  
P. C. Barber ◽  
J. Gregory ◽  
M. C. Sheppard ◽  
P. M. Stewart
Keyword(s):  
Epithelial Cells ◽  
Lamina Propria ◽  
Hormone Receptors ◽  
Rat Kidney ◽  
Distal Colon ◽  
Hydroxysteroid Dehydrogenase ◽  
Neuroendocrine Cells ◽  
Rat Colon ◽  
Mrna Levels

In the rat kidney 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) maintains normal in vivo specificity for mineralocorticoid receptor (MR) by converting the active steroid corticosterone to inactive 11-dehydrocorticosterone, leaving aldosterone to occupy the MR. Clinical observations support the hypothesis that 11 beta-HSD also protects the distal colonic MR from glucocorticoid excess. We have measured 11 beta-HSD mRNA and activity along the rat colon and have analyzed the distribution of 11 beta-HSD, MR, and glucocorticoid receptor (GR) mRNA within rat distal colon using in situ hybridization. Levels of 11 beta-HSD mRNA (1.7 and 3.4 kb) and activity were higher in distal vs. proximal colon, paralleling reported MR mRNA levels. Within the distal colon mucosa both 11 beta-HSD immunoreactivity and mRNA was observed in cells in the lamina propria but not in epithelial cells. MR mRNA was present in surface epithelial cells, but was also colocalized with the same 11 beta-HSD-expressing cells in the lamina propria. In contrast GR mRNA was more uniformly distributed. The localization of MR mRNA to nonepithelial cells in the lamina propria, possibly neuroendocrine cells, suggests that mineralocorticoid-regulated sodium transport across colonic epithelial cells may also involve a paracrine mechanism. As with the kidney, exposure of active mineralocorticoid to the MR in these cells in the lamina propria is dictated by 11 beta-HSD in an autocrine fashion.

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

scholarly journals Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes

2016 ◽  
Vol 94 (4) ◽  
pp. 408-415 ◽  
Author(s):  
Xiaoyuan Han ◽  
Sonali Shaligram ◽  
Rui Zhang ◽  
Leigh Anderson ◽  
Roshanak Rahimian
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Intermediate Stage ◽  
Diabetic Rats ◽  
Female Rats ◽  
Diabetic Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Oxide Synthase

Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.

scholarly journals Do sex steroids regulate glutamine synthesis with age?

2002 ◽  
Vol 282 (1) ◽  
pp. E215-E221 ◽  
Author(s):  
Lionel Verdier ◽  
Yves Boirie ◽  
Sebastien Van Drieesche ◽  
Michelle Mignon ◽  
Rene-Jean Begue ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Sex Steroids ◽  
Tibialis Anterior Muscle ◽  
Female Rats ◽  
Female Wistar Rats ◽  
Endocrine Status ◽  
Key Enzyme ◽  
Reproductive Endocrine ◽  
Glutamine Synthesis

Glutamine synthetase, a key enzyme in the production of glutamine, is known to be induced by glucocorticoids and preserved in skeletal muscle during aging, but the effect of other steroids, such as sex steroids (progesterone, estradiol), is unknown in vivo. The aim of this study was to determine whether progesterone or estradiol plays a role in the regulation of glutamine synthetase (GS) with aging. The effects of glucocorticoids and sex steroids on muscle GS activity and mRNA expression were measured in adult (6–8 mo; n = 7 in each group) and aged (26 mo; n= 10 in each group) female Wistar rats after adrenalectomy (ADX), ovariectomy (OV), or both (ADXOV) and were compared with those in sham-operated (Sham) control rats. In tibialis anterior muscle, ADX noticeably decreased both GS activity and expression irrespective of age (50–60%; P < 0.05), whereas OV had no effect at either age. Progesterone and estradiol replacement had no effect on the recovery of muscle GS response in either ADX or OV rats, regardless of age. In contrast, heart GS activity was decreased by ADX in aged animals only. These results suggest that the reproductive endocrine status of female rats does not affect muscle GS activity either in muscle or in heart, in young or aged animals, and that the heart GS response to steroids may be differently regulated in aged rats.

scholarly journals 2,4,6-Tribromophenol Exposure Decreases P-Glycoprotein Transport at the Blood-Brain Barrier

2019 ◽  
Vol 171 (2) ◽  
pp. 463-472 ◽  
Author(s):  
Andrew W Trexler ◽  
Gabriel A Knudsen ◽  
Sascha C T Nicklisch ◽  
Linda S Birnbaum ◽  
Ronald E Cannon
Keyword(s):  
Blood Brain Barrier ◽  
Ex Vivo ◽  
Female Rats ◽  
Brain Barrier ◽  
Transport Activity ◽  
Fish Food ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Male And Female Rats

Abstract 2,4,6-Tribromophenol (TBP, CAS No. 118-79-6) is a brominated chemical used in the production of flame-retardant epoxy resins and as a wood preservative. In marine environments, TBP is incorporated into shellfish and consumed by predatory fish. Food processing and water treatment facilities produce TBP as a byproduct. 2,4,6-Tribromophenol has been detected in human blood and breast milk. Biologically, TBP interferes with estrogen and thyroid hormone signaling, which regulate important transporters of the blood-brain barrier (BBB). The BBB is a selectively permeable barrier characterized by brain microvessels which are composed of endothelial cells mortared by tight-junction proteins. ATP-binding cassette (ABC) efflux transporters on the luminal membrane facilitate the removal of unwanted endobiotics and xenobiotics from the brain. In this study, we examined the in vivo and ex vivo effects of TBP on two important transporters of the BBB: P-glycoprotein (P-gp, ABCB1) and Multidrug Resistance-associated Protein 2 (MRP2, ABCC2), using male and female rats and mice. 2,4,6-Tribromophenol exposure ex vivo resulted in a time- (1–3 h) and dose- (1–100 nM) dependent decrease in P-gp transport activity. MRP2 transport activity was unchanged under identical conditions. Immunofluorescence and western blotting measured decreases in P-gp expression after TBP treatment. ATPase assays indicate that TBP is not a substrate and does not directly interact with P-gp. In vivo dosing with TBP (0.4 µmol/kg) produced decreases in P-gp transport. Co-treatment with selective protein kinase C (PKC) inhibitors prevented the TBP-mediated decreases in P-gp transport activity.

Sex differences in hepatic fatty acid uptake reflect a greater affinity of the transport system in females

1992 ◽  
Vol 263 (3) ◽  
pp. G380-G385 ◽  
Author(s):  
D. Sorrentino ◽  
S. L. Zhou ◽  
E. Kokkotou ◽  
P. D. Berk
Keyword(s):  
Plasma Membrane ◽  
Fatty Acid ◽  
Transport System ◽  
Fatty Acid Uptake ◽  
Surface Expression ◽  
Female Rats ◽  
Acid Uptake ◽  
Fatty Acid Binding ◽  
Male And Female Rats

In this study, we examined the hypothesis that the reported sex difference in hepatic free fatty acid (FFA) uptake involves the putative FFA transport system, the plasma membrane fatty acid binding protein (FABPpm). In hepatocytes isolated from both male and female rats, initial [3H]oleate uptake velocity reflected transmembrane influx and not subsequent metabolism and was a saturable function of the unbound oleate concentration. Although Vmax values were similar (61 +/- 2 vs. 65 +/- 5 pmol.min-1.5 x 10(4) cells-1 for females and males, respectively), the apparent Km was significantly smaller in females (40 +/- 4 vs. 90 +/- 11 nM; P less than 0.05), reflecting faster influx velocities in female cells over a range of unbound oleate concentrations. The oleate efflux rate constant was also greater in females (0.280 +/- 0.014 vs. 0.198 +/- 0.020 min-1; P less than 0.05) despite their greater hepatic content of cytosolic FABP. Finally, despite the greater rates of transmembrane FFA flux in female hepatocytes, the surface expression of FABPpm was virtually identical in the two sexes (2.5 +/- 0.5 vs. 2.4 +/- 0.4 microgram/10(6) cells). Collectively, these data indicate that at FFA-to-albumin ratios occurring in vivo the plasma membrane of female hepatocytes transports oleate bidirectionally at a greater rate than that of male hepatocytes. A sex-related difference in the functional affinity of FABPpm for FFA appears the most likely explanation for the greater oleate uptake in females.

scholarly journals Neurokinin B and the Control of the Gonadotropic Axis in the Rat: Developmental Changes, Sexual Dimorphism, and Regulation by Gonadal Steroids

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4818-4829 ◽  
Author(s):  
F. Ruiz-Pino ◽  
V. M. Navarro ◽  
A. H. Bentsen ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Sex Steroids ◽  
Developmental Stages ◽  
Female Rats ◽  
Sex Steroid ◽  
Adult Males ◽  
Neurokinin B ◽  
Male And Female Rats ◽  
Gonadotropic Axis ◽  
Key Aspects

Abstract Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, have recently emerged as important regulators of reproduction; NKB has been proposed to stimulate kisspeptin output onto GnRH neurons. Accordingly, NKB has been shown to induce gonadotropin release in several species; yet, null or even inhibitory effects of NKB have been also reported. The basis for these discrepant findings, as well as other key aspects of NKB function, remains unknown. We report here that in the rat, LH responses to the NK3R agonist, senktide, display a salient sexual dimorphism, with persistent stimulation in females, regardless of the stage of postnatal development, and lack of LH responses in males from puberty onward. Such dimorphism was independent of the predominant sex steroid after puberty, because testosterone administration to adult females failed to prevent LH responses to senktide, and LH responsiveness was not restored in adult males treated with estradiol or the nonaromatizable androgen, dihydrotestosterone. Yet, removal of sex steroids by gonadectomy switched senktide effects to inhibitory, both in adult male and female rats. Sexual dimorphism was also evident in the numbers of NKB-positive neurons in the arcuate nucleus (ARC), which were higher in adult female rats. This is likely the result of differences in sex steroid milieu during early periods of brain differentiation, because neonatal exposures to high doses of estrogen decreased ARC NKB neurons at later developmental stages. Likewise, neonatal estrogenization resulted in lower serum LH levels that were normalized by senktide administration. Finally, we document that the ability of estrogen to inhibit hypothalamic Tac2 expression seems region specific, because estrogen administration decreased Tac2 levels in the ARC but increased them in the lateral hypothalamus. Altogether, our data provide a deeper insight into relevant aspects of NKB function as major regulator of the gonadotropic axis in the rat, including maturational changes, sexual dimorphism, and differential regulation by sex steroids.

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Female Rats ◽  
Male Rats ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Male And Female ◽  
Male And Female Rats ◽  
Arterial Contractility

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

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