CORTICOSTEROID-UMSATZ UND CORTICOSTEROID-PRODUKTION BEI RATTEN UNTER DER BEHANDLUNG MIT ANABOLEN STEROIDEN

1965 ◽  
Vol 48 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Herbert Schriefers ◽  
Gerlinde Scharlau ◽  
Franzis Pohl

ABSTRACT After the administration of anabolic steroids to adult female rats in daily doses of 1 mg per animal for 14 days, the following parameters were investigated: the rate of the Δ4-5α-hydrogenase-catalyzed cortisone reduction in liver slices and microsomal fractions, the adrenal weight and the in vitro corticosterone production rate. Among the steroids tested, only 17α-methyl-testosterone and 17α-ethyl-19-nor-testosterone were effective in lowering significantly cortisone reduction rate by liver slices with concomitant decreases in microsomal Δ4-5α-hydrogenase-activity. Testosterone, 19-nor-testosterone, 17α-ethinyl-19-nor-testosterone, 17α-methyl-17β-hydroxy-androsta-1,4-dien-3-one and 1-methyl-17β-hydroxy-androst-1-en-3-one were ineffective or only slightly effective. Adrenal weight and absolute corticosterone production rate (μg/60 min per animal) were decreased after treatment with 17α-methyl-testosterone, 17α-ethyl-19-nor-testosterone and 1-methyl-17β-hydroxy-androst-1-en-3-one. Corticosterone production was decreased with 17α-ethinyl-19-nor-testosterone in spite of an unchanged adrenal weight. The relative corticosterone production rate (μg/60 min · 100 mg adrenal) was in any cases unaffected. According to these results there exists – with the exception of 17α-ethinyl-19-nor-testosterone – a strict parallelism between corticosteroid turnover and corticosterone production rate: unchanged turnover is correlated with unchanged corticosterone production rate, while a decreased turnover is correlated with decreased adrenal activity. The protein-anabolic effect of certain anabolic steroids may be partly due to an anti-catabolic action of these compounds resulting from a decreased corticosteroid inactivation and production rate. Possible mechanisms by which anabolic steroids may affect corticosteroid-balance are discussed.

1968 ◽  
Vol 59 (2) ◽  
pp. 325-334
Author(s):  
Herbert Schriefers ◽  
Hanns-Georg Hoff ◽  
Franzis Pohl

ABSTRACT In experiments with male rats the in vivo effects of thyroxine (T4) and triiodothyronine (T3) on the following parameters were investigated: the microsomal Δ4-5α-hydrogenase activity of the liver, the adrenal weight and the in vitro corticosterone production rate. Either thyroid hormone leads to the known increase in the cortisone reduction rate. However, there are two different mechanisms underlying this effect. While the effect of T4 after two or three days of treatment is due to an increase in the production of reduced NADP by the liver cell with no change in the Δ4-5α-hydrogenase activity (McGuire & Tomkins 1959), treatment for only two days with T3 causes an increase in microsomal activity. The activity of the microsomal preparation without additions is zero for both the control and the T3 treated animals. If increasing quantities of NADP are added together with glucose-6-phosphate and glucose-6-phosphate dehydrogenase, then for each addition of NADP up to the maximum value the activity of the Δ4-5α-hydrogenase of the treated animals is always considerably higher by the same percentage than that of the controls. With animals possessing low Δ4-5α-hydrogenase activity treatment with T3 leads to a greater percentage increase in the enzyme activity than with animals having higher hydrogenase activities. There exists a very close correlation (r = 0.94) between hydrogenase activity and its percentage increase due to T3 administration. The regression-line indicates that with hydrogenase activities greater than 12 T3 is without effect. This leads to the view that the hepatic action of T3 is to promote steroid hydrogenation up to a fixed turnover rate. Although the increase in the adrenal weight was the same with either thyroid hormone, only T3, not T4, was simultaneously effective in raising corticosterone production rate in vitro. Thus, an increase in the adrenal weight is not in any case the expression of an enhanced hormone secretion rate. The fact that the administration of T4 significantly increases Δ4-5α-hydrogenase activity and adrenal weight without concomitant increase in corticosterone production rate must be regarded as evidence against the assumption that the adrenal effect of T4 is simply the consequence of the primary acceleration of corticosteroid turnover in the liver.


1976 ◽  
Vol 83 (3) ◽  
pp. 604-620 ◽  
Author(s):  
B. P. Lisboa ◽  
M. Holtermann

ABSTRACT In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20β-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20β-hydroxy-4-pregnen-3-one to progesterone. Since a hepatic 20β-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20β-hydroxy-4-pregnen-3-one in these animals. Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20β-hydroxy-4-pregnen-3-one with uterine tissue: 20β-hydroxy-5α-pregnan-3-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3α,20β-diol, 4-pregnene-3α,20β-diol and 4-pregnene-3β,20β-diol. The conversion of 20β-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus. 20β-hydroxy-5β-pregnan-3-one is the first C21-metabolite with a 5β(H)-configuration isolated in the rat uterus, which indicates the presence of 5β-reductase in this tissue.


2005 ◽  
Vol 82 (5-6) ◽  
pp. 245-255 ◽  
Author(s):  
Rafael Fernández-Fernández ◽  
Manuel Tena-Sempere ◽  
Víctor M. Navarro ◽  
María L. Barreiro ◽  
Juan M. Castellano ◽  
...  

1964 ◽  
Vol 46 (1) ◽  
pp. 89-94 ◽  
Author(s):  
Herbert Schriefers ◽  
Ulrich Herborn ◽  
Franzis Pohl

ABSTRACT In liver slices of alloxandiabetic rats the rate of the δ4-5α-hydrogenase-catalyzed cortisone reduction is diminished. The decrease is more pronounced in females than in males; in male rats diabetes causes a significant increase in the δ4-5α-hydrogenase-activity present in microsomal fractions, while in diabetic females the activity of this enzyme is within the normal range. Since with microsomal fractions obtained from livers of diabetic rats and supplemented with a TPNH-generating system the rate of hydrogenation of cortisone is unchanged or even elevated it is concluded that the decreased cortisone reduction in diabetic liver slices cannot be accounted for by a lowered activity of the microsomal δ4-5α-hydrogenase but can be explained by the inability of the diabetic liver cell to supply sufficient TPNH for a normal cortisone reduction rate.


1985 ◽  
Vol 107 (1) ◽  
pp. 9-13 ◽  
Author(s):  
S. E. Inkster ◽  
R. N. Clayton ◽  
S. A. Whitehead

ABSTRACT The effects of neonatal monosodium l-glutamate (MSG) treatment on pituitary responsiveness to LH-releasing hormone (LHRH) and on pituitary LHRH receptors have been investigated in the intact adult female rat. Three- to four-month-old rats treated with MSG (4 mg/g body wt) on days 2, 4, 6, 8 and 10 after birth had significantly reduced ovarian and pituitary weights, showed an absence or disruption of ovarian cyclicity after puberty, and had significantly higher concentrations of serum prolactin despite normal levels of LH. In-vitro pituitary LH responses to LHRH were in the normal range for one group of treated animals whilst in a second group the LH responses were markedly enhanced. In contrast, the total number of pituitary LHRH receptors were significantly reduced in all MSG-treated animals showing that the increased pituitary responsiveness of MSG-treated animals is not attributable to an increase in pituitary LHRH receptors. J. Endocr. (1985) 107, 9–13


2000 ◽  
Vol 165 (3) ◽  
pp. 569-577 ◽  
Author(s):  
J Svensson ◽  
S Lall ◽  
SL Dickson ◽  
BA Bengtsson ◽  
J Romer ◽  
...  

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.


2006 ◽  
Vol 188 (3) ◽  
pp. 435-442 ◽  
Author(s):  
P W F Hadoke ◽  
R S Lindsay ◽  
J R Seckl ◽  
B R Walker ◽  
C J Kenyon

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.


2010 ◽  
Vol 104 (3) ◽  
pp. 1286-1300 ◽  
Author(s):  
Jonathan S. Carp ◽  
Ann M. Tennissen ◽  
Jennifer E. Liebschutz ◽  
Xiang Yang Chen ◽  
Jonathan R. Wolpaw

The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12–27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms.


1951 ◽  
Vol 7 (4) ◽  
pp. 344-348 ◽  
Author(s):  
ANITA M. MANDL ◽  
S. ZUCKERMAN

The ovaries and adrenal glands of an adult rat hypertrophy after either ovarian or muscle tissue is homografted into the animal. The ovarian weight/body weight and adrenal weight/body weight ratios become significantly higher than those of normal adult female rats derived from the same colony. Anaesthesia also appears to lead to a transitory increase in the weight of the adrenals. The possibility that the ovaries respond to certain non-specific conditions, in the same general way as do the adrenal glands, is discussed.


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