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At least 253 records · Page 14Linked to original sources
PubMed2000

Steroid sulfatase inhibitor alters blood pressure and steroid profiles in hypertensive rats.

Our hypothesis is that the steroid sulfatase gene (Sts) may indirectly contribute to the modulation of blood pressure (BP) in rats with genetic hypertension. The steroid sulfatase enzyme (STS) catalyzes the conversion of estrone sulfate, dehydroepiandrosterone sulfate, cholesterol sulfate and glucocorticoid sulfates to their active nonconjugated forms. This causes the elevation of biologically active steroids, such as glucocorticoids, mineralcorticoids as well as testosterone, which may lead to increased BP. The main objective was to examine the effects of a steroid sulfatase inhibitor on blood pressure and steroid levels in rats with hypertensive genetic backgrounds. Three treatment groups, 5-15 weeks of age were used: controls, estrone and STS inhibitor (estrone-3-O-sulfamate), (n=8 per group). BP was taken weekly by tail cuff, and serum testosterone (T), estrogens (E), and plasma corticosterone (C) levels were measured by radioimmunoassay. BP was significantly reduced by the STS inhibitor in the strains with genetically elevated BP. Also the inhibitor alone significantly reduced plasma corticosterone in all strains compared to estrone treatment with a concomitant as well as significant rise in estrogens and reduction in testosterone and body weight.

Animals↗
PubMedDate not supplied

Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors.

Steroid sulfatase (STS) regulates the formation of active steroids from systemic precursors, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS). In breast tissues, this pathway is a source for local production of estrogens, which support the growth of endocrine-dependent tumours. Therefore, inhibitors of STS could have therapeutic potential. In this study, we report on substituted chromenone sulfamates as a novel class of non-steroidal irreversible inhibitors of STS. The compounds are substantially more potent (6- to 80-fold) than previously described types of non-steroidal inhibitors when tested against purified STS. In MCF-7 breast cancer cells, they inhibit STS activity with IC(50) below 100 pM. Importantly, the compounds also potently block estrone sulfate-stimulated growth of MCF-7 cells, again with IC(50) below 100 pM. For one compound, we also observed a lack of any estrogenic effect at high concentrations (1 microM). We also demonstrate for the first time that STS inhibitors can block the DHEAS-stimulated growth of MCF-7 cells. Interestingly, this cannot be achieved with specific inhibitors of the aromatase, suggesting that stimulation of MCF-7 cell growth by DHEAS follows an aromatase-independent pathway. This gives further justification to consider steroid sulfatase inhibitors as potential drugs in the therapy of breast cancer.

Arylsulfatases↗
PubMed2004

Preparation of steroid antibodies and parallel detection of multianabolic steroid abuse with conjugated hapten microarray.

A conjugated hapten microarray based on miniature immunoassay for fast and multiplex detection of anabolic steroids is reported for the first time. This preliminary study investigated the possibility of using a microarray technology as a multisteroid detection assay. The microarray system used eight monoclonal antibodies raised against three steroid conjugates, 4-androsten-4-chloro-17beta-ol-3-one, 1,5alpha-androsten-1beta-methyl-17beta-ol-3-one, and 5beta-androsten-1-en-17beta-ol-3-one, which were conjugated to BSA by the active ester method. In addition to 4 commercial conjugated haptens, 18 steroid-BSA conjugates were synthesized and from all these a conjugated hapten microarray was fabricated. The analyzed substances included 42 types of anabolic steroid reference materials and 28 positive urine samples. Of these, 24 anabolic steroids and 12 positive urines were successfully detected.

Anabolic Agents↗
PubMed2003

Renal transplant recipient attitudes toward steroid use and steroid withdrawal.

Although steroid avoidance and withdrawal in renal transplant recipients (RTR) are actively being evaluated by physicians, the attitudes of recipients toward steroid use have not been systematically studied in the modern era. We conducted a confidential written survey of single-organ adult RTR pertaining to prednisone-related side-effects. Recipients were asked which drug they felt maximized graft life, which drug they wished to avoid if graft life was unaffected, and which drug they had most compliant with. They also rated 16 common immunosuppressive-related side-effects on a Likert scale with 1 meaning complete disagreement and 10 complete agreement with their own prednisone-attributed experience. A comparison of responses based on RTR demographic characteristics was made by ANOVA or chi-square analysis with Bonferroni correction. The questionnaire was completed by 223 recipients, of whom 93% were primary recipients, 57% were cadaveric organ recipients, and 69% were white people, 7% black people, and 23% Asian people. Age at transplant, age at survey and time since transplant were 41.5 +/- 11, 47.5 +/- 11 and 6.0 +/- 5 yr, respectively. For the entire group, overall side-effect profile for prednisone was rated as 6.1 +/- 3 on the Likert scale, while efficacy was rated as 7.3 +/- 3. If offered monotherapy, 67% preferred a calcineurin-inhibitor (CI), 23% mycophenolate mofetil (MMF)/azathioprine (AZA), and 10% prednisone. When asked which drug they would like to discontinue, 19% chose CI, 16% MMF/AZA, and 65% prednisone. Most recipients felt that CI was the most efficacious drug (80%), followed by MMF/AZA (12%), and prednisone (8%). The side-effects reported as most common were unacceptable weight gain (5.8 +/- 3) and bone/joint disease (5.3 +/- 3). The least common side-effects were blood disorders (2.2 +/- 2) and cancer (2.3 +/- 2). Black people were more likely than non-black people to report developing diabetes (p = 0.02), blood disorders (p = 0.003) and headaches (p = 0.003) as a result of prednisone use. Males reported more liver damage (p = 0.01) while females reported more body fat (p = 0.01) and fluid retention (p = 0.006). RTR >5 yr post-transplant reported more infections (p = 0.008), skin/hair problems (p = 0.02), gastrointestinal irritation (p = 0.02), and bone disease (p = 0.02) compared with RTR <1 yr. Donor source and recipient age did not determine any responses. If given a 'risk-free' choice, the majority of recipients prefer withdrawal of steroids over other agents. Demographic data may be used to predict prednisone-related side-effects and guide steroid use in this population. Study designs related to steroid withdrawal should account for patient preferences in this context.

Black or African American↗
PubMed1975

Hormonal control of Luteal 20alpha-Hydroxy steroid dehydrogenase and delta5-3beta-hydroxy steroid dehydrogenase during luteolysis in the pregnant rat.

Treatment of pregnant rats with human chorionic gonadotrophin, luteotrophin (luteinizing hormone), luteotrophin-releasing hormone, prostaglandin F2alpha, aminoglutethimide, or by foetoplacental removal or hysterectomy achieved a common multiple-response pattern, namely increased activity of luteal 20alpha-hydroxy steroid dehydrogenase with decreased activity of delta5-3beta-hydroxy steriod dehydrogenase and release of delta4-3-oxo steroids in vitro. 2. Similar effects of foetoplacental removal are noted in pregnant mice. 3. Gonadotrophin induced lower activities of 20alpha-hydroxy steroid dehydrogenase, except at the very end of pregnancy, and partly inhibited the induction caused by foetoplacental removal. 4. The results suggest that existence of a placental factor that restrains these changes until the end of normal pregnancy, which is produced in amounts proportional to the number of placentae and is conveyed to the ovary via the blood. 5. This factor was not replaced by prolactin. 6. It is argued that neither placental lactogen nor pituitary luteotrophin participate in the induction of 20alpha-hydroxy steroid dehydrogenase at late pregnancy in the rat. 7. Aminoglutethimide induced 20alpha-hydroxy steroid dehydrogenase only in late pregnancy. This was partly reversed by progesterone, wholly reversed by progesterone plus oestrogen, and did not involve the pituitary.

Aminoglutethimide↗
PubMed2000

A novel flow cytometric steroid hormone receptor assay for paraffin-embedded breast carcinomas: an objective quantification of the steroid hormone receptors and direct correlation to ploidy status and proliferative capacity in a single-tube assay.

Semiquantitative estimation of steroid hormone receptors by immunohistochemistry applied to paraffin sections is common practice in surgical pathology. Flow cytometric (FCM) analysis of estrogen receptor (ER) and progesterone receptor (PR) levels provides a faster and more objective quantitative assay. However, a major problem in such FCM analyses of solid tumor samples is the admixture of tumor cells with normal epithelial, stromal, and inflammatory cells. The aim of the underlying study was to investigate the applicability of a recently developed multiparameter flow cytometric methodology for the accurate estimation of the fraction of steroid hormone receptor-positive tumor cells and to explore whether this multiparameter approach allows the detection of specific, clinically relevant subsets of tumors, based on a combination of ploidy level, steroid hormone receptor status, and cell cycle characteristics. For this purpose, samples of 42 breast cancer patients, from which routine immunohistochemistry for ER and PR also was available, were analyzed. From each case, a cell suspension was prepared from the paraffin block by applying a heating and short pepsin digestion step to 50-microm-thick sections. These cell suspensions were double-immunostained for cytokeratin to identify the epithelial cells, and ER or PR, whereas DNA was quantitatively stained with propidium iodide using an optimized protocol. In the entire group of breast tumors, the percentages of ER- and PR-positive cells were registered in the epithelial subfraction, in combination with DNA ploidy and S phase fraction (SPF). A significant correlation was found between the fraction of hormone receptor-positive cells as found by the immunohistochemical and FCM procedures. For ER, a correlation coefficient of r = .87 was found, and for PR r = .62, both P < .0001. It became clear that all the diploid breast tumors had more than 30% tumor cells positive for ER with a SPF lower than 10%, whereas aneuploid tumors contained on average a smaller percentage of steroid hormone receptor-positive cells, and simultaneously an SPF greater than 10%. Our results show that this multiparameter FCM analysis allows an objective and reproducible quantification of the fraction of steroid hormone receptor-positive cells in the relevant epithelial cell compartment in relation to DNA ploidy status and proliferative capacity in a single-tube assay.

Breast Neoplasms↗
PubMed2004

Comparison of oral and depot intra-muscular steroids in assessing steroid-responsiveness in COPD.

Non-compliance or euphoria may limit the usefulness of prednisolone tablets in assessing steroid-responsiveness in chronic obstructive pulmonary disease (COPD). Depot intra-muscular methyl-prednisolone (imMP), producing a plateau steroid effect over two weeks, may be more reliable. Following two weeks of placebo, twenty-seven COPD patients (mean FEV 1 43% predicted) participated in a two-week randomised, double-blind, placebo-controlled, parallel-design trial taking either 120 mg imMP with placebo tablets or placebo injection with prednisolone 30 mg daily. After each period, post-bronchodilator FEV 1, forced vital capacity (FVC), inspiratory capacity (IC) and six-minute walking distance (6MWD) were assessed and patients completed both quality-of-life scores (St. George's 30 and Short Form 36) and mood scores (Hospital Anxiety and Depression scores and Altman's Self-rating Mania Scale). There were no significant changes in 6MWD, quality of life or mood scores after either type of steroids and no change in lung function after imMP. By contrast, there were small mean improvements in lung function on oral prednisolone (mean FEV 1, FVC and IC increased by 100, 320 and 150 ml, respectively). Only the improvement in FVC was significantly greater after prednisolone compared with imMP. Single depot intra-muscular injections of steroids have no advantage over oral daily prednisolone in testing steroid-responsiveness in COPD patients.

Administration, Oral↗
PubMed1985

Evidence for involvement of cytochrome P-450-linked oxygenase system in the conversion of C21-steroids to delta 16-C19-steroids catalyzed by pig testicular microsomes.

Formation of androstadienone or androstadienol, a delta 16-C19-steroid, from progesterone or pregnenolone is catalyzed by the so-called delta 16-C19-steroid synthesizing enzyme in the pig testicular microsomes. The enzyme activity was also present in the testicular microsomes prepared from neonatal pig. The enzyme activity was considerably inhibited by CO, and such cytochrome P-450 inhibitors as SU 8000, SU 10603, and metyrapone. delta 16-C19-Steroid synthesizing enzyme activity was extracted from the testicular microsomes by sodium cholate in potassium phosphate buffer, pH 7.4, containing EDTA and dithiothreitol, and the solubilized enzyme activity was partially purified by DEAE-cellulose column chromatography. It was shown by reconstitution of the enzyme activity that delta 16-C19-steroid synthesizing enzyme is a cytochrome P-450-linked oxygenase system dependent on cytochrome P-450-reductase and cytochrome b5. In particular, cytochrome b5 was an essential component for the activity of delta 16-C19-steroid synthesizing enzyme.

Animals↗
PubMed2005

Steroid withdrawal syndrome during steroid tapering in childhood acute lymphoblastic leukemia: a controlled study comparing prednisone versus dexamethasone in induction phase.

Children with acute lymphoblastic leukemia (ALL) receive as part of induction therapy a 4-week course of high-dose glucocorticoid, which is either abruptly discontinued or shortly tapered. The aim of this study was to evaluate the signs and symptoms of steroid withdrawal syndrome and performance status (according to Lansky scale) during the 9-day tapering period and 1 week after withdrawal of the steroid in 63 children randomly allocated to receive prednisone or dexamethasone as part of induction treatment according the AIEOP ALL 2000 protocol. Twenty of 28 (75%) patients on dexamethasone versus 18 of 35 (51.4%) on prednisone (P < 0.05) developed at least one steroid withdrawal symptom during the study period. Three or more symptoms were observed in 39.3% (11/28) of the dexamethasone group and 8.6% (3/35) of the prednisone group (P < 0.05). Dexamethasone patients developed clinical signs earlier (within 3 days from the steroid tapering) than symptomatic prednisone patients. In the prednisone group, the symptoms were less severe and the performance status was higher (P < 0.05). Steroid withdrawal morbidity in ALL children during induction is a frequent and clinically relevant complaint. A more gradual (for dexamethasone) or a more prolonged (for prednisone) tapering might be suggested.

Adolescent↗
PubMed1977

Radioimmunoassay of anabolic steroids: an evaluation of three antisera for the detection of anabolic steroids in biological fluids.

Recently developed radioimmunoassays (RIA) for the analysis of anabolic steroids and their metabolites in biological fluids were tested for cross-reactivity with other types of steroids. Results show that the degree of desirable cross-reactivity within the two classes or orally active anabolic steroids vary widely and that the antiserum for 19-Nortestosterone (the active principle of intramuscular preparations) has a very high degree of undesirable cross-reactivity with components of oral contraceptives. Single and multiple dose studies in human volunteers demonstrate that the detection level and degree of retrospectivity are likewise variable but that the test easily detects most anabolic steroids during treatment. At the present time, the combination of the three antisera for the assay of a sample appears to be a relatively rapid and economic method for screening large numbers of samples in situations where doping control of anabolic steroids is required. The importance of utilizing physico-chemical means for identification of RIA potential positives is emphasized.

Anabolic Agents↗
PubMed2001

Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy.

Rapid amelioration of hypercholesterolemia by LDL apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

Adolescent↗
PubMed1984

Reversible steroid dementia in patients without steroid psychosis.

Six patients developed dementia-like cognitive changes that appeared to result from administration of steroid medications. Four of the patients never showed symptoms of steroid psychosis; the remaining two continued to show steroid dementia well after their steroid psychoses had resolved. The dementia was characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance. All six patients eventually recovered normal mental status following discontinuation or reduction of steroid medications. Larger prospective studies are needed to determine the prevalence and nature of the syndrome.

Adult↗
PubMed1975

Inhibition of placental 3beta-hydroxy-steroid dehydrogenase by naturally occurring steroids. A potential mechanism regulating oestrogen synthesis from unconjugated precursors.

We have proposed that inhibition of placental steroid 3-sulphatase by endogenous steroids may regulate oestrogen synthesis during human pregnancy. The possibility that an additional regulatory mechanism, involving the placental 3beta-hydroxy-steroid dehydrogenase (SDH), may also be operative has now been examined. Inhibitory effects of naturally occurring steroids on SDH activity were determined from the reduction in initial rate of conversion of 3H-dehydroepiandrosterone to non-digitonin precipitable products by 10 000 x g supernatant from homogenates of human term placentae. The apparent Km for dehydroepiandrosterone was 0.33 x 10(-6) M. delta4-3-Oxo products of SDH action (4-androstene-3,17-dione, app. Ki=0.60x10(-6) M; progesterone, app. Ki=1.5x10(-6) M) were the most potent inhibitors and appeared to act non-competitively. Delta5-3beta-Hydroxy alternative substrates were less inhibitory and in the case of pregnenolone (app. Ki=4.5x10(-6) M) behaved competitively. 11beta-, 16alpha-, 17alpha- or 21-hydroxylation and epimerization of 3beta- or 17beta-hydroxyl functions of inhibitors decreased their activity. It is concluded that inhibition of both sulphatase and SDH by endogenous steroids may provide complementary methods of regulating placental oestrogen synthesis in vivo. The SDH mechanism may regulate oestrogen synthesis from unconjugated precursors, either formed within the placenta or derived from the circulation. The major potential inhibitors appear to be delta4-3-ketones, acting non-competitively, and formed within the placenta. In the sulphatase mechanism alternative substrates of extraplacenta origin, acting competitively, are the major potential inhibitors controlling utilization of conjugated precursors.

Androstanes↗
PubMed1993

Brain area specific differences in the effects of neuroactive steroids on the GABAA receptor complexes following acute treatment with anaesthetically active steroids.

Regional differences in the effects of neuroactive steroids on the GABAA receptor complex have been demonstrated in vitro (1-3). In order to elucidate if a regionally different modulation of the GABA-binding site also occurs after acute steroidal treatment, in the present study the effects of systemically applied progesterone (10 mg/kg body wt) and its metabolite 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-THP) (2 mg/kg body wt) on the specific [3H]muscimol binding to the GABA-binding site was evaluated using membrane fractions prepared from five different brain areas of ovariectomized rats. The receptor density (mumol/kg protein) was not affected in all brain areas investigated by treatment with 3 alpha, 5 alpha-THP but was enhanced selectively in the frontal cortex and hippocampus of progesterone-treated animals. A decrease of affinity was observed in medulla after application of progesterone or 3 alpha, 5 alpha-THP, in contrast to the hypothalamus, which was the single region exhibiting an increase of affinity after steroidal administration. In the frontal cortex and hippocampus only the injection of progesterone reduced the affinity, whereas in cerebellum both steroidal treatments were incapable of affecting the affinity. These regional differences in response to the GABA-binding site to acutely applied progesterone and 3 alpha, 5 alpha-THP are consistent with the existence of heterogeneous populations of GABAA receptor-coupled steroid-binding sites.

Anesthetics↗
PubMed1975

Experimental effects of steroids and steroid withdrawal on cerebrospinal fluid absorption.

The authors studied the effects on cerebrospinal fluid (CSF) absorption of chronic administration and acute withdrawal of steroids in dogs. CSF absorption was measured by determining the amount of isotope (indium 111DTPA) recovered over a 4-hour period after injection into the cisterna magna. Resistance to CSF absorption was estimated by determining rates of low of Ringer's lactate infusion into the cisterna magna over a range of pressure gradients between CSF and sagittal sinus. Steroid withdrawal was associated with a marked reduction in CSF absorption and an increase in resistance to CSF flow. Dogs on steroids also showed reduced CSF absorption although the reduction was not statistically significant when compared with controls. The results are discussed in terms of possible mechanisms of action of steroids on CSF absorption, the etiology of the benign intracranial hypertension syndrome and the use of steroids and in the control of intracranial hypertension.

Adrenal Cortex Hormones↗
PubMed1975

Steroid spectrum in human urine as revealed by gas chromatography. I. Qualitative analysis of C19--C2102-3 steroids.

C19C21O2 steroids of urine can be analyzed under isothermal conditions by gas chromatography after a pretreatment consisting of mild acid hydrolysis, simultaneous extraction with toluene (or, in the case of of C21O3 steroids, enzymatic hydrolysis followed by ether extraction), a short purification step and the formation of derivative. Separation of acetyl derivatives could be achieved by three columns: 3%SE-30,1.3%NGS and 3%QF-1. These were needed because the separation of 3alpha-hydroxy-5alpha-androstan-17-one from 3alpha-hydroxy-5beta-androstan-17-one and that of 3alpha-20alpha-dihydroxy-5beta-pregnane from 3alpha, 20alpha-dihydroxy-5alpha-pregnane could be accomplished only in the NGS fluid phase and QF-1 stationary phase, respectively. At the same time, this method gives information on the secretion of anabolic androgenic steroids and on the secretion and metabolism of progesterone and 17-hydroxy-progesterone in the human body. The application of a retention-index system specified for the steroid skeleton and substituents offers the possibility to correlate retention times to molecular structure, which facilitates the identification of problematic metabolites. Steroid spectra as shown by gas chromatography seem to be a promising tool in the early diagnosis of pregnancy on the basis of the increase in the excretion of 3alpha-20alpha-dihydroxy-5beta-pregnane.

Androstanes↗
PubMed2003

Inhibition of estrone sulfate-induced uterine growth by potent nonestrogenic steroidal inhibitors of steroid sulfatase.

The present study describes the biological in vitro and in vivo evaluation of 2-methoxy derivatives of estrogenic inhibitors of steroid sulfatase, namely 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)-1,3,5 (10)-estratrien-17beta-ols. The addition of the 2-methoxy group conserves the potent inhibitory effect on steroid sulfatase activity (IC(50)s of 0.024 and 0.040 nM) while removing the estrogenic action. Using an ovariectomized mouse model, we show that the first generation of steroid sulfatase inhibitors tested, 3-sulfamoyloxy-17alpha-p-tert-butylbenzyl(or benzyl)estra-1,3,5 (10)-trien-17beta-ols and estrone-3-O-sulfamate, are estrogenic compounds stimulating estrogen-sensitive uterine growth. Interestingly, the 2-methoxy-3-sulfamoyloxy-17alpha-benzylestra-1,3,5 (10)-trien-17beta-ol (7) has no estrogenic activity but efficiently blocks (s.c. and p.o.) uterine growth induced by estrone sulfate, which is converted into estrone and then estradiol by steroid sulfatase and type 1 17beta-hydroxysteroid dehydrogenase, respectively. This report clearly shows that a steroid sulfatase inhibitor can efficiently block estrogen action from the inactive precursor estrone sulfate, in vitro and in vivo.

Animals↗
PubMed1989

Steroid binding activity is retained in a 16-kDa fragment of the steroid binding domain of rat glucocorticoid receptors.

The steroid binding domain of the rat glucocorticoid receptor is considered as extending from amino acids 550 to 795. However, such a synthetic protein (i.e. amino acids 547-795; Mr approximately 31,000) has been reported to show very little affinity for the potent synthetic glucocorticoid dexamethasone. We now disclose that digestion of steroid-free rat glucocorticoid receptors with low concentrations of trypsin yields a single species, of Mr = 16,000, that is specifically labeled by dexamethasone 21-mesylate. This 16-kDa fragment retains high affinity binding for [3H]dexamethasone that is only approximately 23-fold lower than that seen with the intact 98-kDa receptor. Analysis of the protease digestion patterns obtained both with trypsin and with lysylendopeptidase C allowed us to deduce the proteolytic cleavage maps of the receptor with these enzymes. From these protease maps, the sequence of the 16-kDa fragment was identified as being threonine 537 to arginine 673. These results show that glucocorticoid receptor fragments smaller than 34 kDa do bind steroids and that the amino acids Thr537-Arg673 constitute a core sequence for ligand binding within the larger steroid binding domain. The much slower kinetics in generating the 16-kDa fragment from affinity-labeled receptors suggests that steroid binding causes a conformation change in the receptor near the cleavage sites.

Amino Acid Sequence↗