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PubMed2003

Weight changes after renal transplantation: a comparison between patients on 5-mg maintenance steroid therapy and those on steroid-free immunosuppressive therapy.

After renal transplantation (RTx), an increase in body weight (BW) is usually observed, in which corticosteroids may play an important role. However, the effects of a low maintenance dosage of corticosteroids on BW have not been studied longitudinally in RTx patients. The aim of this study was to compare changes in BW after RTx in patients on steroid- or steroid-free immunosuppressive therapy and to assess the relationship between post-transplant weight changes and other potentially important factors. The charts of 123 RTx patients (72 male, 51 female) were retrospectively examined for BW changes in the first 5 years after RTx. Sixty-six patients were on 5-mg maintenance steroid dose and 57 patients underwent steroid-free immunosuppression. Mean post-transplant BW gain was 3.0+/-5.3 kg after 6 months, 3.9+/-6.2 kg after 1 year and 6.2+/-8.6 kg after 5 years. Weight gain in the first year after RTx was related neither to maintenance- nor to cumulative steroid dose, age, gender, occurrence of rejection, or renal function. Weight gain was, however, significantly related to pre-transplant BMI and dialysis modality. After the first year, weight gain was significantly and positively related only to the cumulative steroid dose. The course of weight gain in the first year after RTx turned out to be independent from factors such as maintenance- or cumulative steroid dose, age, gender, occurrence of rejection, and renal function; weight gain was, however, dependent on pre-transplant BMI and dialysis modality. After the first year, the weight course was significantly affected by cumulative steroid dose.

Acute Disease↗
PubMed2003

The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome.

Childhood nephrotic syndrome (NS) is frequently characterized by a relapsing course. There is no uniform agreement about the precise stage at which a steroid-sparing agent should be introduced to control the disease. In order to evaluate the treatment strategies and outcome of steroid-sensitive NS over the last 2 decades, a retrospective notes review was undertaken in a cohort of children treated at Great Ormond Street Children's Hospital between 1980 and 2000. From a population of 863 children with NS referred, 509 had frequently relapsing or steroid-dependent disease and 261 children received at least one steroid-sparing agent. Cyclophosphamide was the first choice in 178 patients and in 114 no further steroid-sparing agent was needed. Levamisole was prescribed as the first steroid-sparing agent for 65 children and disease control was achieved in 30%. Cyclosporin A was prescribed in 61 children and sustained remission was induced in 69%. It is concluded that cyclophosphamide is a potent agent in inducing sustained remission in steroid-sensitive NS. Levamisole and cyclosporin A have emerged as attractive steroid-sparing agents. Complications and major side effects of treatment are infrequent but occasionally fatal.

Adolescent↗
PubMed2003

Septic arthritis following intra-articular steroid injection of the knee--a survey of current practice regarding antiseptic technique used during intra-articular steroid injection of the knee.

Septic arthritis is a potential catastrophic complication of intra-articular steroid injection. There is lack of evidence regarding the precautions that should be taken to avoid such a complication, as well as how often it is encountered. The aim of this study was to evaluate the antiseptic precautions taken during intra-articular steroid injection of the knee in the United Kingdom (UK), and estimate how often septic arthritis is encountered by health professionals in the UK following steroid injection of the knee. A questionnaire was posted to 100 orthopaedic surgeons, 100 rheumatologists and 50 general practitioners (GPs), asking them about the cases of septic arthritis following intra-articular steroid injection of the knee that they encountered during their practice and the precautions they take when injecting knees. The response rate was 76.4%; 57.6% of the respondents used alcohol swabs to clean the skin, and the remaining 42.4% used chlorhexidine or Betadine. Only 16.3% used sterile towels to isolate the injection site. There were 32.5% of respondents who routinely used sterile gloves when injecting, and a total of 46.6% used either sterile or non-sterile gloves. Also, 91.1% changed needles between drawing the steroid and injecting it into the joint. Only 24 respondents (12.6%) had encountered septic arthritis after steroid injection of the knee (18 once, 3 twice, 2 three times, 1 several times). We concluded that septic arthritis post intra-articular steroid injection of the knee is probably rare. There is a wide variation in the precautions taken to avoid such a complication. However, the trend seems to be towards minimal use of antiseptic techniques. Further large prospective studies are needed to determine how frequently septic arthritis of the knee is encountered post steroid injection, and the exact precautions that should be taken to avoid it.

Adult↗
PubMed1983

Effects of ACTH on steroidogenesis in bovine adrenocortical cells in primary culture--increased secretion of 17 alpha-hydroxylated steroids associated with a refractoriness in total steroid output.

The long-term effects of ACTH on steroidogenesis in bovine adrenocortical cells maintained in primary culture have been investigated. Cells in monolayer culture were incubated in the presence or absence of ACTH for up to 72 h, and the steroid content of the incubation medium was assayed at 12 h intervals. During the first 12 h, adrenocortical cells incubated in the presence of ACTH (10(-9) M and 10(-6) M) produced substantially more cortisol and corticosterone than did cells incubated in the absence of ACTH. The production of steroidogenic intermediates such as pregnenolone, progesterone, and 17 alpha-hydroxypregnenolone, as well as 17 alpha-hydroxyprogesterone, 11-deoxycortisol, and 11-deoxycorticosterone also was increased by short-term (12 h) treatment with ACTH. Thereafter, corticosteroid production by cells incubated in the continued presence of ACTH decreased in a time and concentration dependent fashion. The maximal rate of cortisol production by cells incubated in the presence of ACTH (10(-9) M and 10(-6) M) for 72 h was only one third that of cells incubated in the presence of ACTH for 12 h. More dramatically, by 36 h, corticosterone secretion by cells incubated in the presence of ACTH (10(-6) M) declined to less than 20% of that of nontreated cells, and the production of 11-deoxycorticosterone was no longer detectable. ACTH also induced refractoriness in the production of other C21-steroids (pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyprogesterone, and 11-deoxycortisol) as well as of C19-steroids (dehydroepiandrosterone, androstenedione, and 11 beta-hydroxyandrostenedione). The ACTH-induced refractoriness in the production of C21-steroids lacking a 17 alpha-hydroxyl group occurred earlier than that of 17-hydroxylated C21-steroids. Despite the decline in total corticosteroid production, the long term effect of ACTH was to enhance the relative secretion of 17 alpha-hydroxylated steroids and C19-steroids. Adrenocortical cells incubated for 72 h in the presence of ACTH continued to secrete cortisol, 17 alpha-hydroxyprogesterone, 11-deoxycortisol, and 11 beta-hydroxyandrostenedione in increased amounts. In fact, 11-deoxycortisol became a major secretory product of the ACTH-refractory adrenocortical cell. These results are indicative that ACTH acts in diverse manners on the bovine adrenocortical cell to affect corticosteroid secretion. The initial stimulation of corticosteroid production appears to be reflective of an increase in overall substrate (cholesterol) utilization and probably is mediated, in part, by an increase in cholesterol side chain cleavage activity. The secretion of 17 alpha-hydroxysteroids and C19-steroids is enhanced further by an action of ACTH to increase 17 alpha-hydroxylase activity and possibly also 17,20-lyase activity. The ACTH-induced refractoriness in corticosteroid production, on the other hand, appears to result primarily from a decline in precursor (cholesterol) utilization.

Adrenal Cortex↗
PubMedDate not supplied

Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma.

It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device.

Administration, Inhalation↗
PubMed1991

Regulation of steroid and steroid sulfate production and aromatase activity in cultured human granulosa-luteal cells.

The regulation of the production of steroids and steroid sulfates and the activity of aromatase in human luteinized granulosa cells were investigated. The cells were cultured for 48 h in the presence or absence of hCG and FSH. Basal production of pregnenolone (Pre, 0.3 +/- 0.03 ng/micrograms protein) and progesterone (P, 19.3 +/- 1.7 ng/micrograms protein) were high compared with that of other steroids beyond P in the steroidogenic pathway. The concentration of 17 alpha-hydroxyprogesterone (17-OHP) was lower 0.17 +/- 0.06 ng/micrograms and that of other steroids in the 4-ene and 5-ene pathways and steroid sulfates less than 0.05 ng/micrograms. Both hCG and FSH (100 ng/ml) stimulated the production of Pre and P 3- to 5-fold, but only minimal stimulation of other steroids and steroid sulfates was observed. Aromatase activity of granulosa-luteal cells was measured from the rate of formation of 3H2O from 1 beta-[3H]androstenedione (1 beta[3H]A) after exposing the cells to hCG, FSH or estradiol (E2) for 48 h. Basal aromatase activity was relatively low, but hCG and FSH stimulated aromatase 8- and 4-fold, respectively. The incubation of granulosa-luteal cells with E2 did not affect basal aromatase activity, but E2 augmented FSH-stimulated aromatase 1.4-fold (P less than 0.025). The results suggest that there is low 17 alpha-hydroxylase and steroid sulfokinase activity in human granulosa-luteal cells. Aromatase activity in these cells is regulated by both hCG and FSH, and intra-ovarian estrogens may regulate granulosa cell aromatase activity.

Aromatase↗
PubMed1987

Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone.

Studies investigating steroid dose and avascular necrosis of bone (AVN) have found either a weak association or none at all. This quantitative review of published studies has evaluated the effects of steroid dose and bolus steroids on the risk of AVN. 22 papers with sufficient information for analysis were identified. The mean steroid dose for the cohort was plotted against the percentage in whom AVN developed. Total dose was divided into non-bolus (oral) and bolus dose, and doses 1, 3, 6, and 12 months after beginning steroids were tested separately for their association with AVN risk. There was a strong correlation between daily total dose and AVN rate (r = 0.61-0.80). Oral dose was strongly correlated with AVN rate (r = 0.70-0.86), but bolus dose was not associated with AVN risk. This strong association between AVN and steroid dose contrasts with the weak relations found in case-control studies from individual centres in which cases and controls received similar steroid regimens and therefore did not differ greatly in steroid dose. The method of deriving a single exposure level per study and comparing the amount of exposure across studies may be useful in assessing whether a drug's toxicity is dose dependent.

Adrenal Cortex Hormones↗
PubMed2004

Steroid cover for dental patients on long-term steroid medication: proposed clinical guidelines based upon a critical review of the literature.

Based to a great extent upon mainly anecdotal case reports and theory, there is a general acceptance that patients on long-term systemic steroid medication should receive supplementary glucocorticoids or "steroid cover" when undergoing certain types of stressful treatment including dentistry. The theoretical basis to this practice is that exogenous steroids suppress adrenal function to an extent that insufficient levels of cortisol can be produced in response to stress, posing the risk of acute adrenal crisis with hypotension and collapse. The purpose of this paper is to review relevant literature and propose clinical guidelines for dental practitioners. Of numerous reported cases of adrenal crisis following procedural interventions, few stand up to critical evaluation. Other reviewers have reached similar conclusions. A number of studies confirm the low likelihood of significant adrenal insufficiency even following major surgical procedures. Various authors have suggested modified guidelines for management of patients on steroid medications. Patients on long-term steroid medication do not require supplementary "steroid cover" for routine dentistry, including minor surgical procedures, under local anaesthesia. Patients undergoing general anaesthesia for surgical procedures may require supplementary steroids dependent upon the dose of steroid and duration of treatment.

Acute Disease↗
PubMed1998

Steroid acne vs. Pityrosporum folliculitis: the incidence of Pityrosporum ovale and the effect of antifungal drugs in steroid acne.

BACKGROUND: Steroid acne is a folliculitis that can result from systemic or topical administration of steroid, and has been described as showing a similar clinical picture to Pityrosporum folliculitis, but there have been few reports about the incidence of Pityrosporum ovale and the effect of antimycotic drugs in steroid acne and other acneiform eruptions. Our purpose was to describe the association between steroid acne and P. ovale, and to confirm the superior efficacy of oral antifungal drugs over anti-acne drugs in the treatment of steroid acne. METHODS: The history, clinical features direct microscopy, histopathologic analysis, and therapeutic results of 125 cases with steroid acne or other acneiform eruptions were described and compared. RESULTS: Over 80% of patients with acneiform eruption receiving systemic steroid revealed significant numbers of P. ovale in the lesional follicle. Furthermore, oral antifungal drug (itraconazole) showed significantly better clinical and mycologic effects than any other group of medications used in this study. CONCLUSIONS: Steroid acne and other acneiform eruptions showing discrete follicular papules and/or pustules localized to the upper trunk and acneiform facial skin lesions associated with multiple acneiform lesions on the body in the summer period should be suspected as Pityrosporum folliculitis. In addition, oral antifungal drugs recommended for Pityrosporum folliculitis; however, it will require a larger case-control study to confirm the superiority of antifungal therapy over anti-acne treatment.

Acne Vulgaris↗
PubMed2005

Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation.

Two steroid-sparing immunosuppressive regimens were prospectively compared in recipients of simultaneous pancreas-kidney transplants, one did not include steroids at all and the other included steroids for the first 3 months following transplantation. All patients received rabbit anti-thymocyte globulin, mycophenolate mofetil (MMF) and cyclosporine. Fifty patients were randomised in an open-label, single center and prospective study. The incidence of biopsy-proven acute rejection during the first 12 months after transplantation was the primary endpoint of the study. The incidence of biopsy-proven acute rejection was 4% in both groups. No statistically significant difference in patient (96 and 100%), kidney (96 and 100%) or pancreas (84 and 92%) survival was observed 1 year after transplantation in the steroid avoidance and steroid withdrawal groups, respectively. The total number of adverse events (including severe ones), length of hospitalization and infectious episodes did not differ between groups. Blood glucose and insulin levels, lipid profile and hemoglobin A1C levels did not differ statistically between the two groups. However, the 1-year serum creatinine level was significantly higher in the steroid avoidance group (132 vs. 114 micromol/L; p = 0.02). Steroid avoidance and steroid withdrawal 3 months after transplantation are safe and effective regimens for diabetic patients with pancreas-kidney transplants.

Adolescent↗
PubMed1985

Steroid sulfotransferases and steroid sulfate sulfatases: characteristics and biological roles.

This review discusses the biological roles of steroid sulfotransferase enzymes (ST's) and steroid sulfate sulfohydrolases (sulfatases) mainly in mammalian tissues. In addition, some consideration is given to certain characteristics of these enzymes and, where possible, to their biological control. A considerable number of ST's of varying specificities, substrate affinities, and kinetics appear to exist. Several of these possess the properties of regulatory enzymes. ST's which act upon estrogen in reproductive tissues, such as uterus, are of particularly high affinity, appear to be under some biological control, and may exert important effects upon estrogen action. Although biosynthetic pathways involving steroid sulfate intermediates have been described, their importance is difficult to determine. The presence of an esterified sulfate group on a steroid molecule may markedly affect the action of enzymes, such as hydroxylases, upon the steroid structure in both a qualitative and quantitative sense. The number of different steroid sulfatases is not well understood. A sterol sulfatase present in the female reproductive tract appears capable of destabilizing the sperm head membrane by hydrolyzing sterol sulfates necessary for its integrity, and hence enabling the fusion of sperm and ovum. Other sulfatases may utilize blood-borne steroid sulfates for the ultimate production of estrogen which, in fetal membranes, could play a role in parturition and, in breast tumours, could function as a growth promoting agent. Brain sulfatases could possibly produce steroid hormones for purposes of tissue differentiation and (or) feedback control mechanisms, but this is not firmly established.

Adrenal Cortex↗
PubMed2006

Severe nasal polyposis and its impact on quality of life. The effect of a short course of oral steroids followed by long-term intranasal steroid treatment.

OBJECTIVES: Nasal polyposis is not a life-threatening disorder but has a great impact on the quality of life. Steroids constitute the first line of treatment of nasal polyps. The aims of this study were to evaluate the quality of life in nasal polyp patients after: (1) a short course of oral steroids; and (2) a long-term treatment with intranasal steroids. METHODS: Patients with severe nasal polyps received either oral prednisone (n = 60) or no steroid treatment (control group, n = 18) for 2 weeks. Patients treated with steroids were also followed-up and evaluated after 12, 24, and 48 additional weeks with intranasal budesonide treatment. RESULTS: Patients with nasal polyps showed worse scores on all SF-36 domains, except for physical functioning, compared to the Spanish general population. After two weeks, patients treated with oral prednisone demonstrated a significant improvement (p < 0.05) in all impaired QoL domains compared to both control group and baseline. The mental component summary (51.0 +/- 1.2, p < 0.05) and physical component summary (51.0 +/- 0.9, p < 0.05) were improved compared to both control group and baseline. The improvement of all SF-36 domains was sustained by intranasal budesonida (p < 0.05) after 12, 24, and 48 weeks. Nasal obstruction, sense of smell, and polyp size also improved after both the oral short course and the intranasal long-term steroids treatment (p < 0.05). CONCLUSION: These results suggest that the treatment with a short-course of oral steroids improves the quality of life of patients with severe nasal polyps and that this effect is maintained by a long-term treatment with intranasal steroids.

Administration, Intranasal↗
PubMed1990

Identification of lysine 134 in the steroid-binding site of the sex steroid-binding protein of human plasma.

The sex steroid-binding protein of human plasma SBP (or sex hormone-binding globulin, SHBG) was specifically inhibited with the alkylating affinity label, 17 beta-[[( 2-14C]bromoacetyl)oxy]-5 alpha-androstan-3-one. The natural ligand, 5 alpha-dihydrotestosterone, was shown to protect against inactivation and labeling. The steroid-binding activity of the protein was abolished when approximately 1 mol of label was incorporated into 1 mol of dimeric SBP. In order to identify and locate the labeled amino acid in the steroid-binding site, the steroidal portion of the bound label was first removed and the protein was digested with Achromobacter protease and subdigested with trypsin. Seven radioactive peptides were isolated, sequenced, and found to contain the common sequence QVSGPLTSXR. Residue X was identified as lysine-134 from the SBP amino acid sequence (Walsh, K. A., Titani, K., Kumar, S., Hayes, R., and Petra, P. H. (1986) Biochemistry 25, 7584-7590). The results indicate that only 1 of the 2 lysine-134 residues in the homodimer was labeled. This suggests that the steroid-binding site is constructed from an association of the two subunits in an AB to BA "sandwich" configuration with lysine-134 residue of one subunit on one surface near the D-ring and the lysine-134 of the other subunit at the opposite end of the steroid, or well away from the steroid-binding site. Although the nature of the data does not allow description of a specific role for lysine-134, its proximity to the 17 beta-OH of the steroid nucleus suggests participation in the binding process through direct or indirect hydrogen bonding.

Affinity Labels↗
PubMed1989

Blood steroid levels in the goldfish: measurement of six ovarian steroids in small volumes of serum by reverse-phase high-performance liquid chromatography and radioimmunoassay.

A reliable and rapid technique for the measurement of estradiol-17 beta, testosterone, progesterone, 17 alpha-hydroxyprogesterone, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, and cortisol by reverse-phase high-performance liquid chromatography and radioimmunoassay in single female goldfish serum samples of 50 microliters was developed. The steroids were extracted with Sep-Pak C18 cartridges after heat treatment. While estradiol-17 beta was assayed directly after extraction, the other steroids were separated on a mu Bondapak C18 stainless-steel column with acetonitrile:water (53:47, v/v) in 17 min under isocratic conditions, and then quantitated by specific radioimmunoassays. The technique was validated and was shown to be highly accurate, precise, sensitive, and specific for measuring those particular ovarian steroids in goldfish serum. The steroid levels measured in this way were not significantly different from those measured after separation on a Nova-Pak C18 column with methanol:water (56:44, v/v), where all the individual steroids could be completely resolved during a 40-min run. With this technique, the steroid levels in the serum of the goldfish during the secondary yolk stage, the tertiary yolk stage, and at 0 hr after ovulation were determined. While estradiol-17 beta was found to be significantly higher in the tertiary yolk stage, testosterone was significantly higher in the secondary yolk stage than in the other two stages. There was no significant difference in the levels of cortisol, 17 alpha-hydroxyprogesterone,17 alpha,20 beta-dihydroxy-4-pregnen-3-one, and progesterone among the three stages. We conclude that the technique is particularly useful for assaying multiple steroids in very small volumes of biological fluids.

Animals↗
PubMed1988

Steroid sulfohydrolase activity in human chorion. I. Interactions of other steroids with estrone sulfate as substrate.

Human chorion contains steroid sulfohydrolase activity and synthesizes free estrogens from estrone sulfate (E1S). We hypothesized that the free estrogen thus formed may influence the contractility of the adjacent myometrium in late pregnancy. In this study we measured the abilities of various steroids and steroid conjugates to influence the hydrolysis of E1S by the 105,000 x g pellet of chorion tissue obtained from women after spontaneous onset of labor and vaginal delivery and from women delivered by cesarean section before labor onset. No differences were found in tissues obtained before or after the onset of labor. None of the steroids increased the rate of hydrolysis. Several unconjugated steroids caused significant inhibition, but only at concentrations well beyond physiological ranges in maternal or fetal blood. However, conjugated steroids had marked inhibitory effects at circulating concentrations. At equimolar concentrations with the E1S substrate, the sulfoconjugates of dehydroepiandrosterone, pregnenolone, and cholesterol caused 27 +/- 1% (+/- SE), 64 +/- 1%, and 40 +/- 1% inhibition, respectively. These results were confirmed using a tissue explant system. Using enzyme inhibition kinetic analysis, we determined that the inhibition by dehydroepiandrosterone sulfate was non-competitive, with Ki = 8.7 +/- 1.7 mumol/L. The inhibition by pregnenolone sulfate was competitive, with Ki = 1.6 +/- 0.4 mumol/L, and that by cholesterol sulfate was primarily noncompetitive, with Ki = 7.4 +/- 1.2 mumol/L. We conclude that there is significant interaction among sulfurylated steroids that may influence local free estrogen synthesis within human chorion. This interaction may affect the contractility of the late pregnancy myometrium.

Chorion↗
PubMed1982

Effects of gonadal steroid hormones on the hypothalamo-pituitary-liver axis in the control of sex differences in hepatic steroid metabolism in the rat.

The site of action of gonadal hormones in the regulation of hepatic steroid metabolism was investigated by measuring the effects of (i) implantation of estradiol into the pituitary gland or anterior hypothalamus of males and (ii) subcutaneous injection of a synthetic androgen in differentiated male and female rats. The hepatic responses measured in vitro were 5 alpha-reduction, and 6 beta- and 16 alpha-hydroxylation of androstenedione. After intrapituitary or intrahypothalamic implantation of oestradiol, 5 alpha-reductase activity increased and 6 beta- and 16 alpha-hydroxylase activity decreased in males relative to the enzyme activities of cholesterol-implanted animals, indicating a feminizing effect of the oestrogen. This effect could not be accomplished by subcutaneous injection of the same oestrogen preparation. Deafferentation had no effect on hepatic steroid metabolism in females, but caused a feminization in males. In addition, subcutaneous treatment of intact females with the synthetic androgen caused masculinization of hepatic steroid metabolism, but was without effect in differentiated animals. Treatment with synthetic androgens had no effect on the hepatic steroid metabolism in differentiated male animals. Subcutaneous injection of a potent synthetic progestagen had little effect on hepatic steroid metabolism in intact females. It is concluded that oestrogen feminizes hepatic steroid metabolism by an action at the hypothalamic-pituitary level and that an intact hypothalamic-pituitary axis is required for the masculinizing action of the synthetic androgen on hepatic steroid metabolism. It is possible that the site of action of androgens is in the anterior hypothalamus or in adjacent areas of the brain.

Androstenedione↗
PubMed1982

Oocyte maturation in the amago salmon (Oncorhynchus rhodurus): in vitro effects of salmon gonadotropin, steroids, and cyanoketone (an inhibitor of 3 beta-hydroxy-delta 5-steroid dehydrogenase).

The effect of partially purified chinook salmon gonadotropin (SG-G100) and a number of steroids on the induction of germinal vesicle breakdown (GVBD) in amago salmon (Oncorhynchus rhodurus) oocytes (with intact follicle layers) was investigated in vitro. SG-G100 was effective only at the highest concentration tested (1 microgram/ml). 17 alpha,20 beta-Dihydroxy-4-pregnen-3-one (17 alpha,20 beta-diOHprog) was the most potent maturation-inducing steroid tested, followed by 17 alpha-hydroxyprogesterone. Testosterone or deoxycorticosterone (DOC) enhanced the rate of GVBD in response to SG-G100. DOC also enhanced the response to 17 alpha,20 beta-diOHprog but testosterone was without effect, suggesting that DOC has a direct action on the oocyte while testosterone probably acts at the level of the follicle. Estradiol-17 beta had no effect on GVBD in response to SG-G100 or 17 alpha,20 beta-diOHprog. The action of SG-G100 was shown to be dependent on the synthesis of a second delta 4 steroidal mediator of maturation since cyanoketone, a specific inhibitor of 3 beta-hydroxy-delta 5-steroid dehydrogenase, completely abolished the maturational effects of the gonadotropin and pregnenolone but not delta 4 steroids. Radioimmunoassay of media in which oocytes were induced to mature in vitro with SG-G100 revealed significantly elevated levels of progesterone and 17 alpha,20 beta-diOHprog. Estradiol-17 beta levels, high in control media, were only elevated twofold by SG-G100. Levels of the two progestogens were extremely low or nondetectable in media in which oocytes were incubated with cyanoketone, while estradiol-17 beta levels remained high. These results are discussed in relation to other evidence indicating that 17 alpha,20 beta-diOHprog is the naturally occurring maturation-inducing steroid of amago salmon. The role of other steroid hormones, particularly the possible involvement of corticosteroids, in the control of final oocyte maturation in teleosts is explored.

17-alpha-Hydroxyprogesterone↗
PubMed1978

Simultaneous solubilization of steroid hormones I: estrogens and C21 steroids.

The simultaneous solubilization of some estrogens and C21 steroids in aqueous polysorbate 40, tetradecyltrimethylammonium bromide, and sodium lauryl sulfate was studied. The less soluble estrogen estradiol was solubilized independently of the C21 steroids. The micellar solubilities of ethinyl estradiol and both corticosterone and hydrocortisone were independnet of the presence of each other while the solubility of 11alpha-hydroxyprogesterone was enhanced by ethinyl estradiol. The solubilizations of ethinyl estradiol and the two C21 steroids, progesterone and 21-hydroxyprogesterone, were dependent on each other so that a varying amount of the steroid solubilized first was precipitated by an excess of the second steroid. If saturated solutions of the two steroids were mixed, no precipitation occurred. A possible mechanism for the simultaneous solubilization of steroids and its relation to structure are discussed.

Chemistry, Pharmaceutical↗