ENDOCRINE REGULATION OF SEX-DEPENDENT HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN RAT KIDNEY: NADP-DEPENDENT MICROSOMAL 3α- AND 20β-HYDROXYSTEROID DEHYDROGENASE

1977 ◽  
Vol 73 (2) ◽  
pp. 289-300 ◽  
Author(s):  
R. GHRAF ◽  
E. R. LAX ◽  
W. WAGNER ◽  
H. SCHRIEFERS

SUMMARY The NADP-dependent microsomal kidney enzymes, 3α- and 20β-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male: female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary–gonad and pituitary–adrenal systems. Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3α-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5α-dihydrotestosterone (5α-DHT) or 5α-androstane-3α, 17β-diol to hypophysectomized male rats was equally effective in restoring full 3α- and 20β-HSDH activities whereas 5α-androstane-3β, 17β-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5α-DHT. Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective. Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity. The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance.

1978 ◽  
Vol 89 (2) ◽  
pp. 352-358 ◽  
Author(s):  
Edmund Rodney Lax ◽  
Rüdiger Ghraf ◽  
Herbert Schriefers

ABSTRACT Hepatic microsomal 11β-hydroxysteroid dehydrogenase activity is higher in male than in female rat liver. Gonadectomy on day 25 of life only affects the activity in the adult male animal, causing a decrease towards the normal female level. Administration of testosterone to gonadectomized rats of either sex causes the induction of typical male activity levels. On the basis of these experiments, this enzyme activity may be classified as androgen-dependent. However, 11β-hydroxysteroid dehydrogenase differs from other known androgen-dependent activities in that administration of oestradiol to gonadectomized animals of either sex causes a further significant repression of the activity to levels close to the limits of detection. Hypophysectomy on day 50 of life does not affect the activity in 75 day-old male rats, but causes the appearance of typically male activity levels in females. These results indicate that the hypophysis exerts a repressive influence on hepatic 11β-hydroxysteroid dehydrogenase in female rats. The fact that this activity is not influenced by androgen or oestrogen administration once the pituitary has been removed demonstrates the obligatory role of the hypophysis for sex hormone action.


2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  

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


1981 ◽  
Vol 90 (1) ◽  
pp. 53-58 ◽  
Author(s):  
S. M. DONOHOE ◽  
A. J. THODY ◽  
S. SHUSTER

Sexually experienced male rats were used to test the attractiveness of preputial gland odours of female rats. The male rats showed a clear preference for the preputial gland odours of hypophysectomized females given oestradiol benzoate (OB) for 3 or 8 days to those of control rats. Progesterone treatment had no effect on the attractiveness of the preputial gland odours of OB-treated hypophysectomized female rats. Administration of α-MSH for either 3 or 8 days, on the other hand, increased the attractiveness to male rats of preputial gland odours of OB-treated hypophysectomized females and the presence of progesterone produced no further change. When administered alone α-MSH had no effect on the attractiveness of the preputial gland odours. Other pituitary hormones, such as ACTH and prolactin, had no effect on the attractiveness of preputial gland odours of OB-treated hypophysectomized rats when administered for 3[unk]days. An increase in preputial gland size was only seen when OB, progesterone and α-MSH were administered together. It would appear that no relationship exists between the size of the preputial glands and their ability to attract male rats. It is concluded that, while α-MSH and progesterone may be important in controlling growth of the preputial glands, an interaction between α-MSH and oestrogen is more important for regulating the production of sex attractants by the preputial glands.


1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.


1993 ◽  
Vol 294 (1) ◽  
pp. 159-165 ◽  
Author(s):  
P K Srivastava ◽  
D J Waxman

The sex-dependent expression and growth hormone (GH) regulation of rat liver glutathione S-transferase (GST) was examined using oligonucleotide probes that distinguish between closely related class Alpha (Ya1, Ya2, Yc) and class Mu (Yb1, Yb2, Yb3) GST mRNAs [Waxman, Sundseth, Srivastava and Lapenson (1992) Cancer Res. 52, 5797-5802]. Northern-blot analysis revealed that the steady-state levels of GST Ya1, Yb1 and Yb2 mRNAs are 2.5-3-fold higher in male as compared with female rat liver. In contrast, GST Yc and Ya2 mRNAs were expressed at a 2-3-fold higher level in female rat liver. Microsomal GST mRNA did not exhibit significant sex-dependent differences in rat liver. Treatment of male rats with GH by continuous infusion suppressed expression of the male-dominant GST Ya1, Yb1 and Yb2 mRNAs to levels at or below those found in female rat liver. This suppressive effect of GH was liver-specific, insofar as GH treatment did not alter kidney GST Ya1 mRNA levels. Hypophysectomy increased expression of the male-dominant GSTs, particularly in female rats (e.g. 8-fold elevation of GST Ya1 mRNA). GST Yc mRNA was increased approx. 2-fold in hypophysectomized males, indicating that this mRNA is subject to negative regulation by one or more pituitary-dependent factors. Continuous GH treatment of the hypophysectomized rats suppressed the expression of mRNA of GSTs Ya1, Yb1 and Yb2 when given as a continuous infusion, but not when given by an intermittent (twice daily) GH-injection schedule. Combination of continuous exposure to GH with thyroxine treatment resulted in a more complete suppression of GSTs Ya1, Yb1 and Yb2. In contrast, thyroxine increased the expression of GST Yc in hypophysectomized rats. These studies establish that several Alpha and Mu class GSTs are expressed in a sex-dependent fashion in adult rat liver, where they are regulated by multiple pituitary-dependent hormones through pretranslational mechanisms.


1987 ◽  
Vol 114 (3) ◽  
pp. 350-356 ◽  
Author(s):  
G. Norstedt ◽  
B. Husman ◽  
A. Mode ◽  
P. Eneroth ◽  
U.J. Lewis ◽  
...  

Abstract. The sex differentiated binding 125I-human prolactin (PRL) to rat liver membranes was studied and the present results extend our previous studies on induction of hepatic PRL receptors by growth hormone (GH). In prepubertal female rats, PRL receptor levels are low compared with those in mature female rat livers. Infusion of hGH during one week to 17-day-old female rats resulted in a receptor level typical of adult female rats. The time course of receptor disappearance in male rats treated with hGH was also studied. When the receptor-inducing hormone was removed, receptor levels in hGH-treated male rats returned to the normal level characteristic of male rats after approximately 96 h. The specificity of various GH-like and PRL-like hormones in PRL receptor induction was studied in hypophysectomized rats. The PRL-like hormones were identified by measuring their potency to displace 125I-hPRL from a receptor preparation obtained from female rat livers, and the GH-like hormones were identified by their potency to increase body weight in hypophysectomized rats. Using similar doses of hormones it was found that in vivo administration of growth-promoting peptides (rGH, hGH, bGH) induced PRL receptors, whereas lactogenic hormones (rPRL, hPL) had a very small or no effect on PRL receptor induction. This suggests that binding to a type of GH receptor is the first step in PRL receptor induction.


1973 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
E. C. Griffiths ◽  
K. C. Hooper

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.


1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


1990 ◽  
Vol 5 (3) ◽  
pp. 267-274 ◽  
Author(s):  
I. Porsch Hällstöm ◽  
J.-Å. Gustafsson ◽  
A. Blanck

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.


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