ENZYME ACTIVITY IN KIDNEY, ADRENAL AND GONADAL TISSUE OF RATS TREATED NEONATALLY WITH ANDROGEN OR OESTROGEN

1975 ◽  
Vol 67 (3) ◽  
pp. 317-326 ◽  
Author(s):  
R. GHRAF ◽  
H.-G. HOFF ◽  
E. R. LAX ◽  
H. SCHRIEFERS

SUMMARY A single injection of 300 μg oestradiol benzoate (OEB) or 1·25 mg testosterone propionate (TP) on day 1 of life led to significant changes in the activity of enzymes involved in steroid hormone metabolism in kidney, adrenal and gonadal tissues of adult rats. In the kidney, the enzyme activities of male rats reacted to OEB, but not TP, by the development of normal female levels. With one exception the enzyme activities of the kidney of female rats did not respond to either steroid. In the adrenal of both sexes 5α-reductase reacted to OEB, but not TP treatment, by a fourfold increase in activity. In the ovary all the enzymes investigated responded both to OEB and TP treatment by a fall in activity; 20α-hydroxysteroid dehydrogenase activity fell to undetectable levels. In the testis, OEB and TP treatment led to contrasting effects. With the exception of 5α-reductase all the enzymes tested in this organ responded to OEB by a rise in activity. Where TP had any effect, it produced a slight decrease in activity.

1976 ◽  
Vol 70 (3) ◽  
pp. 409-420 ◽  
Author(s):  
P. SÖDERSTEN

SUMMARY Sex differences in the lordosis response of adult rats to ovarian hormones were studied in a series of experiments. Male rats were less sensitive to oestradiol benzoate (OB, a single injection of 10, 100 or 1000 μg/kg or seven daily injections of 2, 10 or 50 μg/kg) than were female rats. Oestradiol benzoate-primed (10 μg/kg) female, but not male, rats showed dose-dependent responses to progesterone (0·4, 2·0 or 10·0 mg/kg). Male rats responded clearly to progesterone (2 mg/rat) only when primed with a high dose of OB (100 μg/rat). Display of the whole pattern of female sexual behaviour was induced in male rats by treatment with 100 μg OB and 2 mg progesterone. Female rats treated with 1 mg testosterone propionate (TP) on day 4 of life, ovariectomized as adults and tested under the same endocrine conditions as the rats described above, retained behavioural OB sensitivity but responded poorly to progesterone. Evidence is presented that ovarian secretions during development significantly modify the response of neonatally TP-treated and normal female rats to OB in adulthood.


1975 ◽  
Vol 67 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. DE MOOR ◽  
M. ADAM-HEYLEN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN

SUMMARY Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found. Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters. After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.


1977 ◽  
Vol 74 (2) ◽  
pp. 315-NP ◽  
Author(s):  
A. DANGUY ◽  
J. L. PASTEELS ◽  
F. ECTORS

A single injection of 1 mg of a complex of testosterone esters on day 5 of life was used to prepare constantly oestrous rats. Such androgenized female rats were then ovariectomized and submitted to stereotaxical implantation of 1 μg oestradiol benzoate, 5 μg testosterone isobutyrate or, as a control, 10 μg cholesterol in the anterior hypothalamic areas. The effects of the steroids on plasma and pituitary FSH and LH were assessed by radioimmunoassay. As reported previously by us in normal female and male rats, the preoptic–suprachiasmatic area (POA) was able to control synthesis and secretion of both gonadotrophins and did not lose its sensitivity to oestradiol and testosterone in androgenized rats. Evidence for enhanced prolactin secretion in androgenized rats was derived from immunofluorescence studies of the pituitary gland and from histology of the mammary glands. In this respect the condition of the androgenized females was opposite to that of the males. The present work demonstrated that stimulation of prolactin secretion in androgenized female rats resulted from oestrogen action due to permanent oestrus rather than from impairment of hypothalamo-hypophysial relationships. Indeed, prolactin stimulation was suppressed when the androgenized rats were ovariectomized and restored when they were subsequently implanted with oestradiol in the POA.


1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

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.


2001 ◽  
Vol 91 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Christian K. Roberts ◽  
Nosratola D. Vaziri ◽  
R. James Barnard

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.


1974 ◽  
Vol 142 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Pousette

The regulatory mechanisms involved in the control of the nuclear NADPH-dependent 3-ketosteroid 5α-reductase (5α-reductase) activity were studied in liver, kidney and prostate. The substrate used was [1,2-3H]androst-4-ene-3,17-dione (androstenedione) (for liver and kidney) or [4-14C]androstenedione (for prostate). The hepatic nuclear 5α-reductase activity was greater in female than in male rats, was greater in adult than in prepubertal female rats, increased after castration of male rats, but was not affected by treatment with testosterone propionate or oestradiol benzoate. These regulatory characteristics are in part different from those previously described for the hepatic microsomal 5α-reductase. The renal nuclear metabolism of androstenedione, i.e. 5α reduction and 17β-hydroxy steroid reduction, was relatively unaffected by sex, age, castration and treatment with testosterone propionate. However, treatment of castrated male rats with oestradiol benzoate led to a significant increase in the 5α-reductase activity and a significant decrease in the 17β-hydroxy steroid reductase activity. Finally, the nuclear 5α-reductase activity in prostate was androgen-dependent, decreasing after castration and increasing after treatment with testosterone propionate. In conclusion, the nuclear 5α-reductase activities in liver, kidney and prostate seem to be under the control of distinctly different regulatory mechanisms. The hypothesis is presented that whereas the prostatic nuclear 5α-reductase participates in the formation of a physiologically active androgen, 5α-dihydrotestosterone, this may not be the true function of the nuclear 5α-reductase in liver and kidney. These enzymes might rather serve to protect the androgen target sites in the chromatin from active androgens (e.g. testosterone) by transforming them into less active androgens (e.g. 5α-androstane-3,17-dione and/or 5α-dihydrotestosterone).


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sharnikha Saravanan ◽  
Weizhao Zhao ◽  
Kunjan R Dave ◽  
Miguel A Perez-Pinzon ◽  
Ami P Raval

Background: A woman’s risk of a stroke increases exponentially following the onset of menopause, andpost-stroke cognitive decline is a significant consequence of stroke survivors. Our earlier study demonstrated that physical exercise (PE) reduced post-stroke brain injury and improved cognitive functions in male rats. The focus of our study is on the improvement of post-stroke cognitive function in female rats. Methods: Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO; 90 min) and randomly assigned to either PE or sham-PE groups. After 3-5 days, rats underwent sham-PE (0m/min speed) or PE (15m/min speed) for 30 mins either every day (continuous) or alternate day for five times on treadmill. The rats that underwent the alternate day paradigm were treated with ER-β agonist (DPN; 1mg/kg) or vehicle-DMSO immediately following PE/sham-PE sessions to determine the synergistic effect. Twenty-one days after the last PE/sham-PE, rats were tested for hippocampal-dependent contextual fear conditioning and freeze time was measured. Rat brains were processed for histology and infarct area was measured with MCID software. From a separate cohort of rat subjected to PE or sham-PE, brain tissue was harvested for various biochemical assays and mitochondrial enzyme activity measurements. Results: Post-tMCAO continuous PE did not reduce ischemic damage. However, alternate PE regimen with or without ER-β agonist reduced infract volume by 20% (p < 0.05) and 23% (p < 0.05), respectively as compared to no-PE. Similarly, alternate PE showed increased freezing on the second day of fear conditioning by 15% (p < 0.05), indicating improved spatial memory. Individual mitochondrial complex I, II, III and IV enzyme activity measurements demonstrated significant improvement in complex III-IV enzyme activities in the alternate PE treated group as compared to sham-PE. Conclusion: An alternate day PE paradigm and ER-β activation improves post-stroke mitochondrial enzyme activities and cognition in reproductively senescent female rats. Future studies delineating underlying mechanism could help identify therapies to prevent/reduce cognitive decline in menopausal female stroke patients.


1996 ◽  
Vol 271 (3) ◽  
pp. F527-F538 ◽  
Author(s):  
S. C. Borkan ◽  
Y. H. Wang ◽  
K. T. Lam ◽  
P. Brecher ◽  
J. H. Schwartz

In the present study, we provide immunohistochemical and immunologic evidence to localize an abundant, 15.5-kDa protein to the soluble protein fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha 2 mu-globulin (A2 fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reaction, mRNA for A2 was detected in male liver but not in the male kidney. De novo accumulation of the 15.5-kDa protein was observed in the renal cortex of female rats given intravenous injections of purified 19-kDa protein (A2), suggesting intrarenal processing of the larger protein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was determined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which the 15.5-kDa protein was virtually absent: 1) uninephrectomized male rats treated with deoxycorticosterone acetate and salt, 2) male rats subjected to bilateral adrenalectomy, and 3) normal female rats. In the absence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all three models. In female renal cortex, depletion of the 15.5-kDa protein was associated with a rise in heart fatty acid binding protein, an alternative intracellular transporter of fatty acids. These data support the hypothesis that a proteolytic cleavage product of hepatic alpha 2 mu-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in the proximal tubule.


1966 ◽  
Vol 44 (1) ◽  
pp. 95-101 ◽  
Author(s):  
J. R. Beaton ◽  
A. J. Szlavko ◽  
J. A. F. Stevenson

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.


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