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Biomedical subjects

M Oettel

Publications and source records attributed to M Oettel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mechanisms of relaxation of rat aorta in response to progesterone and synthetic progestins.

OBJECTIVE: To compare the acute effects of progesterone, chlormadinone acetate (CMA), norethisterone acetate (NETA) and dienogest (DNG) with those of 17 beta-estradiol (17 beta-E2) on the vascular reactivity of male rat thoracic aorta. METHODS: Aortic rings with or without endothelium were placed in an organ bath for isometric tension recording. The integrity of the endothelium was assessed by the relaxant response of precontracted rings to acetylcholine (1 and 10 microM), which was diminished after mechanical removal of the endothelium. The concentrations of the steroid hormones were 0.01-10 microM. RESULTS: In vessels precontracted with phenylephrine (1 microM), CaCl2 (3 mM) or KCl (30 mM), progesterone, CMA and NETA (10 microM each) an endothelium-independent relaxation of 20-35% resulted, with a maximum response after 20-30 min, while DNG had a negligible effect in all experiments. The same concentration of 17 beta-E2 was twice as potent as the progestins. Indomethacin, the cyclooxygenase inhibitor and glibenclamide, an inhibitor of the ATP-sensitive potassium channels, did not affect the relaxant responses. The antagonists of progesterone receptors J 867 (1 microM) as well as of estrogen receptors ICI 182780 (1 microM) did not counteract the relaxation induced by progesterone and 17 beta-E2, respectively. Progesterone (10 microM) did not interfere with endothelium-dependent acetylcholine-induced relaxation of precontracted aortic rings. Pretreatment of the vessels with the hormones attenuated the maximal contractile response to phenylephrine. In the presence of verapamil (1 microM) or progesterone (10 microM) or 17 beta-E2 (1 and 10 microM) the concentration-response curves for calcium-induced contractions in K(+)-depolarized vessels were shifted to the right, with suppression of the maximum response. CONCLUSIONS: These studies suggest that in addition to 17 beta-E2 the progestins, progesterone, CMA and NETA caused a reduction of vascular tone, probably due to blockade of voltage-dependent and/or receptor-operated calcium channels.

Animals↗
PubMed1997

A comparative study of two levonorgestrel-containing hormone replacement therapy regimens of efficacy and tolerability variables.

OBJECTIVE: To compare the effect of two sequential hormone replacement regimens differing in the dose of levonorgestrel on climacteric symptoms, bleeding pattern and lipid metabolism in postmenopausal women. STUDY DESIGN: In a multicentre, randomized, double-blind, active-treatment-controlled study, 210 postmenopausal women were assessed at the end of treatment cycles 3 and 6. The high-levonorgestrel group was treated with 2 mg estradiol valerate (days 1-21) sequentially combined with 0.25 mg levonorgestrel (days 12-21). The low-levonorgestrel group received the same estrogen regimen (2 mg estradiol valerate, days 1-21), but levonorgestrel was administered sequentially in a dose of 0.15 mg during the last 12 days of the cycle (days 10-21). Statistical analysis by Student's t-test for dependent variables (measured values versus baseline) and independent variables (differences between groups), and the composite t-test method for comparison of both regimens with respect to efficacy, was performed. RESULTS: Both groups were statistically comparable. The trial was completed by 137 subjects. Protocol violations occurred in 38 cases. Thirty-five subjects dropped out during the study, 21 of them because of adverse events. Both treatments were equally effective in the treatment of climacteric complaints. There were no clinically significant changes in body weight, blood pressure, haematological tests, and parameters of clinical chemistry. There was a tendency towards a reduction in bleeding intensity in both groups in the second half of the treatment period. The treatment for six cycles with both regimens significantly (P < 0.05) decreased plasma concentrations of triglycerides (significant in the low-levonorgestrel group only), high-density lipoprotein cholesterol, high-density lipoprotein-3-cholesterol, lipoprotein(a) and apolipoprotein A1. In parallel, the serum concentration of total cholesterol increased significantly in both treatment groups, whereas low-density lipoprotein cholesterol increased significantly in the high-levonorgestrel group only. The changes in high-density lipoprotein-2-cholesterol, and apolipoprotein B did not reach statistical significance. CONCLUSIONS: It can be concluded that both sequential combined oral hormone replacement therapy (HRT) regimens were equivalent with respect to efficacy and tolerability in the treatment of women with climacteric complaints. The preparation with the lower dose of progestin showed a tendency towards a less unfavourable influence on the lipid profile.

Cohort Studies↗
PubMed1997

Novel "scavestrogens" and their radical scavenging effects, iron-chelating, and total antioxidative activities: delta 8,9-dehydro derivatives of 17 alpha-estradiol and 17 beta-estradiol.

Antioxidant effects of delta 8,9-dehydro derivatives of 17 alpha-estradiol and 17 beta-estradiol were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activities. The parent molecules, 17 alpha-estradiol and 17 beta-estradiol as well as estrone and estriol inhibit iron-dependent lipid peroxidation and stimulate total antioxidant activity. In contrast, delta 8,9-dehydro estrogens such as J811, J861, J835, or J851 not only exhibit the antioxidative activities as the parent molecules do but also directly alter the iron redox chemistry and drastically inhibit the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reactions. These in vitro findings indicate that 17 alpha-estradiol as well as 17 beta-estradiol, modified with an additional double bond in the basic structure, trigger more potent antioxidant properties. These results suggest that relatively minor modifications in the chemical structure of estrogenic compounds can enhance antioxidative actions.

Acridines↗
PubMed1997

Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.

Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.

Animals↗
PubMed1997

Measurements of urinary prostaglandins in young ovulatory women during the menstrual cycle and in postmenopausal women.

The purpose of the present work was to study the prostaglandin excretion in young nonpregnant ovulatory women during the menstrual cycle on the one hand and in postmenopausal women on the other hand and to investigate the influence of female sex hormones (estradiol, progesterone) on urinary prostanoid excretion. Urinary excretion rates of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and their metabolites PGE-M (11 alpha-hydroxy-9, 15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3-dinor-TxB2 and 11-dehydro-TxB2 were determined by gas chromatography-triple stage quadrupole mass spectrometry (GC/MS/MS) in 41 young non-pregnant women during the follicular phase and during the luteal phase and in 23 postmenopausal women. Excretion rates of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. In contrast to the young ovulatory women, PGE2 and TxB2 were significantly higher in postmenopausal women. Concerning the other prostaglandins significant differences between these groups of women did not exist. Although serum levels of estradiol and progesterone were different in young and postmenopausal women, sex hormones have not been shown to correlate with prostaglandins. Our data do not suggest sex hormones to be responsible for the difference in the prostaglandin excretion in women of reproductive age and in women in the menopause. Further systematic investigations into age dependency of prostaglandin excretion in women are necessary.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Dehydroepiandrosterone stimulates the estrogen response element.

Studies suggest that the steroid, dehydroepiandrosterone (DHEA) can exert effects directly, in addition to its indirect role serving as a precursor for other steroids such as androgens and estrogens. Because DHEA is one of the most abundant adrenal steroids secreted in man, we investigated the functional activity of DHEA on the classic estrogen response element (ERE) in the presence of the estrogen receptor (ER) in transiently transfected cells. GT1-7 hypothalamic neuronal cells, devoid of the estrogen receptor, were transiently transfected with the estrogen receptor expression plasmid (HEGO) and the estrogen response element luciferase (ERELUC) reporter vector. As expected, a dose-response stimulation of luciferase activity was observed in cells treated with estradiol. Concentrations of estradiol from 10(-10)-10(-6) M resulted in a 136-195 percent increase in luciferase activity compared with control. A dose-response stimulation was also observed in the cells treated with DHEA. A maximum stimulation of 177 percent increase in luciferase activity compared with control was observed with DHEA at a concentration of 10(-5) M. Both the estradiol and DHEA stimulation of ERE luciferase activity was inhibited by the estrogen receptor antagonist, ICI 182,780. The aromatase inhibitor, formestane in combination with estradiol or DHEA had no effect on luciferase activity, suggesting that the effect of DHEA is independent of its conversion to estradiol. Estradiol levels, as measured by ELISA, were appropriately elevated in the estradiol-treated cells but were not significantly different from the control cells in the DHEA-treated cells. These studies suggest a functional in vitro role of DHEA in activating the ERE in the presence of the classic ER.

Androstenedione↗
PubMed1997

[Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations].

Antiandrogens or progestins with an antiandrogenic component usually have only a weak antigonadotropic activity. It is thus possible that the antiandrogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian androgen production. The aim of the four submitted clinical studies of the progestin and antiandrogen dienogest alone (0.5-2 mg/day) or of a combined regimen of ethinylestradiol (0.03 mg) plus dienogest (2 mg) (EE/DNG) was to examine the influence on the serum androgen and SHBG concentrations as well as on the serum FSH, LH, progesterone and 17 beta-estradiol concentrations in young women. Like the progesterone derivatives, dienogest has a relatively low antigonadotropic activity. Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion. Dienogest alone has no significant effects on the serum SHBG and androgen concentrations. Unlike this, the combination of EE plus DNG markedly increases SHBG concentrations (to 2.1-3.7 fold the basal levels). The decrease in serum androgens with total testosterone (by 17 and 40%), free testosterone (by 48 and 54%) and dehydroepiandrosterone sulfate (by 51%) corresponds to the values shown in the literature for other oral contraceptives with modern progestins. EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone (DHT), although the marker of the peripheral transformation from T to DHT, androstanediol glucuronide, is distinctly reduced (by 38%). In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel. Solely the SHBG concentrations, with EE/DNG, as expected, are significantly higher. In a sequential regimen, dienogest, chlormadinone acetate and desogestrel (progestins without binding to SHBG) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone, whereas norethindrone acetate and levonorgestrel (progestins with a strong binding to SHBG) reduce this effect of the estrogen significantly. These results exclude the possibility that the very distinct antiandrogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of androgen.

Adolescent↗
PubMed1996

Are the antioxidative effects of 17 beta-estradiol modified by concomitant administration of a progestin?

OBJECTIVE: Estrogens are known to exhibit antioxidative effects. At present little information exists on the influence of co-administered progestins upon this effect. Therefore we investigated the influence of levonorgestrel, a potent antiestrogenic progestin, on the inhibition of the low-density lipoprotein (LDL) oxidation by 17 beta-estradiol or 17 beta-estradiol valerate in vitro and ex vivo. METHODS: After isolation from blood, the in vitro oxidation of LDL was induced by copper ions and measured continuously by monitoring the formation of conjugated dienes. In 21 female ovariectomized White New Zealand rabbits the antioxidative action of 17 beta-estradiol alone or in combination with levonorgestrel after subcutaneous infusion for 3 days was determined using the copper-induced LDL-oxidation as an endpoint. Eleven postmenopausal women were exposed to sequential estrogen-progestin replacement therapy (day 1-21:2 mg estradiol valerate/day, day 10-21: 0.15 mg levonorgestrel/day). Blood samples were collected at three times: on day 1, on day 10, on day 22 (after the combination phase). The lag time of ex vivo oxidation of LDL, the plasma estradiol and estrone levels were estimated. RESULTS: In the chosen cell-free system, 17 beta-estradiol increased the lag time of the LDL-oxidation in a dose-dependent manner. Levonorgestrel showed neither pro-oxidative nor antioxidative effects when administered alone in different concentrations. Co-administration of different doses of levonorgestrel did not modify the antioxidative action of estrogen either. The two ex-vivo models confirmed these results. In rabbits the co-administered 19-nortestosterone derivative levonorgestrel did not impair or reverse the estradiol-dependent effect. In postmenopausal women the daily oral administration of levonorgestrel in conjunction with 17 beta-estradiol valerate did not diminish the antioxidative action of this estrogen given for the first 9 days. CONCLUSION: The antioxidative potential of estradiol and estradiol valerate is maintained in the presence of levonorgestrel.

Animals↗
PubMed1994

Normal and stable transfected cancer cell lines: tools for a screening of progestogenic, antiprogestogenic and antiglucocorticoid substances.

Synthetic ligands for steroid receptors represent important drugs in the control of fertility and in the therapy of a large variety of endocrinological diseases. In the present study we describe the establishment of different biochemical and molecular biological screening methods. We developed a microtiter plate assay for the induction of the de novo synthesis of alkaline phosphatase in T47D cells as a suitable and fast system for the measurement of actions of progestogenic and antiprogestogenic compounds. We compared several progestogenic activities with relative molar binding affinities (RBA) to the progesterone receptor. The ED50 values for the induction of alkaline phosphatase are in good accordance with RBA to the progesterone receptor. Furthermore, glucocorticoid and antiglucocorticoid effects were measured in the stable transfected breast cancer cell line ZR75/-763AGP-CAT. The construct AGP-CAT contains the glucocorticoid responsible element of the rat alpha-1-acid glycoprotein (AGP) gene with the bacterial chloramphenicol acetyltransferase (CAT) gene. The rat hepatoma Reuber cell line H4-II-E with the tyrosine aminotransferase gene is a further suitable marker of glucocorticoid action and was used as a second model for glucocorticoid activity. Thus, we demonstrated in three cell systems the antiprogestogenic and antiglucocorticoid activities of the model compound mifepristone.

Alkaline Phosphatase↗
PubMed1993

[The endocrinologic profile of metabolites of the progestin dienogest].

Two identified metabolites of the orally active progestin dienogest, the compounds STS 749 (17 alpha-cyanomethyl-11 beta,17 beta-dihydroxy-estra-4,9-dien-3-one) and STS 825 (17 alpha-cyanomethyl-estra-1,3,5(10),9(11)-tetraene-3,17 beta-diol), furthermore 4 microbially formed metabolites and 10 chemically prepared analoga of dienogest were characterized by endocrinological tests. The compounds were investigated for progesterone-receptor binding, progestational and antiprogestational, estrogenic and antigonadotropic activities, furthermore for inhibition of fertility. In no case an increased progestational activity of metabolites or analoga was found, compared to the parent substance. Therefore, it should be excluded, that dienogest acts as a prodrug. Additionally, the dosages necessary to produce the progestational effects are quite similar using oral or subcutaneous application. Therefore, a first-pass effect can be neglected. Regarding the low endocrine side effects of dienogest, the antiprogestational activity may be caused, at least in part, by metabolites.

Androgen Antagonists↗
PubMed1985

Further report on the endocrinological profile of two synthetic estrogens with antifertility properties, STS 456 and STS 593.

Two synthetic estrogens, STS 456 and STS 593, with noteworthy post-coital antifertility properties in the rat were studied for their estrogenic, antiestrogenic, progestagenic, antiprogestagenic, antigonadotrophic, androgenic and antiandrogenic effects in laboratory animals. Beside their weak estrogenic activity which corresponds to their slight affinity to the uterine estrogen receptor in the rat, both steroids show remarkable antiestrogenic effects. No progestagenic, androgenic and antiandrogenic effects were found but STS 593 showed some antiprogestagenic activity. The antigonadotrophic efficacy of STS 456 was relatively high while STS 593 was scarcely active. The results are discussed with respect to possible application of these drugs for interceptive purposes.

Anabolic Agents↗
PubMed1983

Progestagenic and antigonadotrophic activities of STS 557.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was tested for progestagenic activity in rabbits and for ovulation-inhibiting activities in rabbits and rats in comparison with levonorgestrel and, in some cases, with norethisterone acetate or chlormadinone acetate. In the immature rabbit, the endometrium transformation-inducing activity of STS 557 was about 5 times higher than levonorgestrel for both oral and subcutaneous administration. The ovulation-inhibiting effect of STS 557 was 3.5 times higher than that of levonorgestrel in the rabbit after oral administration, and about 7 times higher in the rat. After subcutaneous injection, however, the antiovulatory activity of STS 557 in rats was only about 4% of that of levonorgestrel when the ED 50 were compared.

Administration, Oral↗
PubMed1983

Interceptive activities of STS 557 in rabbits, mice and rats.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

Amine Oxidase (Copper-Containing)↗
PubMed1983

Inhibition of male fertility by STS 557.

To ascertain the effects of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) on the reproductive and endocrine functions, male rabbits were given the substance orally daily over 8 weeks. In doses of 10 and 20 mg STS 557 per animal per day fertility inhibition was accompanied by a decrease of spermatogenesis and sexual activity. At the chosen dose of 5 mg per day, STS 557 caused a decrease of sperm motility, semen fructose content and sterility of the bucks. On the other hand, libido, semen volume, sperm number, sialic acid content in semen, serum LH and testosterone remained unaffected. Concomitant injection of testosterone did not reverse the suppressive effect of STS 557 on fertility. Motility of human sperm was lowered markedly by STS 557 in vitro. The human sperm penetration and pronuclear formation were significantly reduced in the vitro fertilization assay with zona-free hamster eggs. Findings are discussed in view of the development of male contraceptives.

Animals↗
PubMed1983

Long term toxicological studies on the progestin STS 557.

The toxicity of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one (STS 557) was studied by its oral administration of 0.1, 1.0 or 10.0 mg/kg/day to Wistar rats for six months, and of 0.01, 0.1 or 1.0 mg/kg/day to beagle dogs for six months, respectively. Levonorgestrel at a dose of 1.0 mg/kg/day was used as the standard in the dog study. With respect to the progestational activity of the compound the main target organs were the hypophysis, the reproductive organs and the adrenals. Mammary hyperplasia was observed in dogs treated with STS 557 or levonorgestrel at the dose of 1.0 mg/kg/day, but in no case mammary nodules could be detected. At the dose of 1.0 mg/kg/day STS 557 and levonorgestrel were found to increase the plasma insulin response to i.v. glucose in bitches, but neither the mean blood glucose levels nor the glucose utilization were affected. Moreover, during administration of both steroids to dogs temporary changes in serum concentrations of triglycerides and total cholesterol were noted. The results obtained in rats and dogs from functional and morphological investigations did not reveal any toxic side effects of STS 557 on the liver, the kidneys, the bone marrow or on blood coagulation. The effects on the reproductive organs observed following STS 557 especially in dogs are related to both the hormonal effects of the compound and the specific response of the dog to potent progestagens.

Animals↗
PubMed1983

STS 557 as an interceptive in baboons.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) or levonorgestrel was given orally as a single dose of 0.4 mg per animal. Treatment was performed immediately after the 18 h or 6 h mating period. Regarding the 18 h mating period, in 30 control cycles (20 animals) 11 pregnancies (36.7%) and in 20 cycles (16 animals) with levonorgestrel treatment 2 pregnancies (10.0%) were observed. In 80 cycles (31 animals) with STS 557 treatment 7 pregnancies occurred (8.7%). With regard to the 6 h mating period, in 30 control cycles (18 animals) 9 pregnancies (30%) and in 26 cycles (17 animals) with levonorgestrel administration 3 pregnancies were recorded (11.5%). In 50 cycles (21 animals) with postcoital administration of STS 557 only two pregnancies occurred (4%). Therefore, after the 6 h mating period STS 557 showed high interceptive activities in this non-human primate model. In comparison with controls, STS 557 did not decrease the postovulatory rise of plasma progesterone. This finding demonstrates that postcoital STS 557 in the chosen dosage does not suppress ovulation. Repeated STS 557 administration starting early in the follicular phase was without marked influence on cycle characteristics. On the other hand, treatment start in the middle or at the end of the cycle caused cycle lengthening and reduced progesterone levels in some animals.

Animals↗
PubMed1982

Toxicity of the progestagen STS 557 compared to levonorgestrel in beagles after oral administration for 6 months.

Female and male beagle dogs were administered orally STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-13 beta-methyl-gon-4,9(10)-dien-3-one) for 6 months at dose levels of 0.01, 0.1, or 1.0 mg/kg/day, and levonorgestrel at a dose of 1.0 mg/kg/day, respectively. The results mainly confirmed the gestagenic efficacy on the reproductive organs of both compounds acting directly or via the anterior pituitary gland. In contrast to levonorgestrel, STS 557 did not show any androgenic activity, but had slightly estrogenic effects. Neither clinical, functional nor morphological investigations revealed toxic side effects of the drugs on the liver, the kidneys, the bone marrow, or on blood clotting function.

11-Hydroxycorticosteroids↗