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At least 523 records · Page 29Linked to original sources
PubMed1989

Is follicular fluid steroid content representative of follicular steroid secretion?

Nine oestrogen-active (E-A) and seven oestrogen-inactive (E-I) bovine follicles were superfused for 10 h. Levels of oestradiol (E2), testosterone (T) and progesterone (P4) were measured in superfusate and follicular fluid. No correlation between intrafollicular steroid concentrations of E2, T and P4 and the amount of these steroids detected in the superfusate was found in oestrogen-active follicles, i.e. follicular fluid E2, T or P4 levels did not allow for any prediction of superfusate E2, T and P4 concentrations and vice versa. In contrast, E-I follicles showed a close correlation between intrafollicular and superfusate T and P, but not E2 levels. It is speculated that an alteration in intrafollicular regulatory mechanisms might explain the different findings for these two classes of follicles.

Animals↗
PubMed2004

DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis.

OBJECTIVE: Using a rabbit model, we investigated the DNA oxidation injury occurring in bone following steroid administration and focused on the relation between DNA oxidation injury and osteonecrosis. METHODS: Japanese white rabbits weighing about 3.5 kg were injected with a single intramuscular dose of methylprednisolone 4 mg/kg and divided into groups consisting of 10 rabbits each, which were killed after 3, 5 and 14 days (groups A, B and C respectively). As a control, five untreated rabbits (group N) were also studied. An immunohistochemical study of the diaphysis of the proximal femur was conducted using the monoclonal antibody N45.1, which is a highly specific antibody against 8-hydroxy-2'-deoxyguanosine, an index of DNA oxidation injury. Also, using NIH Image freeware, the positive area (8-OHdG %PA) of each group was calculated and the four groups were compared. RESULTS: Osteonecrosis was detected only in group C (70%). N45.1 positivity was noted in bone marrow haematopoietic cells and was particularly marked in groups B and C. 8-OHdG %PA was 1.6 +/- 0.2% in group N, 2.2 +/- 0.4% in group A, 4.8 +/- 0.4% in group B and 5.1 +/- 0.5% in group C, with significantly greater oxidation injury found in groups B and C (P < 0.001). CONCLUSION: Oxidative injury was demonstrated soon after the administration of methylprednisolone in a rabbit model prior to the development of osteonecrosis. This finding may suggest new strategies to prevent steroid-induced osteonecrosis, such as the optimally timed (early) administration of antioxidant agents.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1986

Alterations in sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), and steroid hormone concentrations during pregnancy in rhesus macaques.

Temporal relationships between concentrations of sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), total and free estradiol, total and free testosterone, cortisol, and progesterone were studied in plasma obtained at 1- to 3-day intervals throughout gestation in six rhesus macaques. Concentrations of SBP and CBG were measured by diethylaminoethyl cellulose filter assays. Total and free steroids were estimated by radioimmunoassay and ultrafiltration dialysis, respectively. We found that SBP was elevated between days 30 and 50 and CBG between days 60 and 140; both then declined until term (167 days). Estradiol increased gradually throughout gestation. Testosterone was elevated between days 10 and 40, then declined, and rose slightly in late gestation until approximately 15 days before delivery, when it increased markedly. Free estradiol and testosterone increased dramatically before parturition. Progesterone was elevated between days 25 and 45 and declined to relatively constant levels thereafter. Cortisol was essentially unchanged throughout gestation. Our data show that in the pregnant rhesus, levels of SBP and CBG vary independently of one another, but both decline before term; concentrations of both total and free estradiol and testosterone increase markedly before parturition; in late gestation, elevated estrogen is not associated with increased levels of SBP or CBG (as it is in human females).

Animals↗
PubMed1989

Luteal production of steroids and prostaglandins during simulated early pregnancy in the primate: differential regulation of steroid production by chorionic gonadotropin.

Stimulation of the primate corpus luteum (CL) by endogenous chorionic gonadotropin (CG) in early pregnancy, or by exogenous human (h)CG in simulated early pregnancy, results in a transient elevation of serum progesterone (P) and a persistent elevation of serum 17 beta-estradiol (E). Luteal prostaglandins (PG) may play a role in these responses. The objective of the current study was to correlate luteal PG production and steroidogenic response of CL in vitro with patterns of serum steroids during simulated early pregnancy. CL were removed from rhesus monkeys (n = 26) at 0 h, 9 h, 3 days, 6 days, and 10 days, during prolonged CG exposure of simulated early pregnancy. Dispersed cells were incubated in vitro at 37 degrees C for 8 h. Changes in basal production of P were not significantly correlated with patterns of serum steroids. Maximal stimulation of P production by hCG in vitro (stimulated minus basal) continuously declined (p less than 0.01) from 0 h (means +/- SE, 59.6 +/- 17.9 ng/ml) to 10 days (4.7 +/- 1.8 ng/ml) of simulated early pregnancy. In contrast to patterns of response to hCG, the level of enhancement in P production in response to a maximally stimulatory dose of dibutyryl (db) cyclic adenosine 3',5'-monophosphate (cAMP) declined (p less than 0.05) from 0 h (52.4 +/- 17.6 ng/ml) to 3 days (20.3 +/- 8.4 ng/ml), but was maintained through 10 days (23.7 +/- 11.6 ng/ml) of simulated early pregnancy. As such, desensitization to gonadotropin, which occurred in terms of P production, appears to involve an event subsequent to stimulation of adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1998

A randomized trial comparing cyclosporine and steroids with cyclosporine, azathioprine, and steroids in cadaveric renal transplantation.

BACKGROUND: In renal transplantation, triple-drug therapy (low-dose cyclosporine [CsA] combined with azathioprine plus steroids) has been replacing double-drug therapy (CsA plus steroids) in clinical practice without much evidence in favor of either therapy. Previous trials comparing the two immunosuppressive regimens gave conflicting results. We attempted to determine whether triple therapy is at least equivalent to double therapy. METHODS: A randomized trial was performed in 250 adult cadaveric renal transplant recipients, comparing double therapy (CsA [10 mg/kg/day] plus prednisone) with triple therapy (CsA [6 mg/kg/day] plus azathioprine plus prednisone). The median follow-up time was 930 days. RESULTS: The incidence of acute rejection episodes refractory to treatment was 11% in double therapy and 4% in triple therapy (relative risk reduction: 64%; 95% confidence interval: 5-100%; P=0.035). Patients in the double therapy group required more intensive antirejection treatment, and their pathologic lesions were more severe. The proportion of patients with acute rejection was similar (double therapy: 45% vs. triple therapy: 40%) as was the incidence of chronic renal dysfunction (double therapy: 17% vs. triple therapy: 15.5%), the 4-year graft survival (double therapy: 71% vs. triple therapy: 83%, P=0.089), and patient survival (double therapy: 94% vs. triple therapy: 93%). In 29 patients (23%), 35 episodes of azathioprine-induced leukopenia were recorded, and in 9 of them azathioprine had to be discontinued. The incidence of other adverse events did not differ between the groups. CONCLUSIONS: Triple therapy caused fewer episodes of refractory acute rejection episodes and was as efficacious and safe as double therapy.

Acute Disease↗
PubMed1986

Reduction in murine Langerhans cell ATPase staining following topical but not systemic treatment with steroid and non-steroid immunosuppressants.

The effects on murine Langerhans cells (LC) of steroid and non-steroid immunosuppressive drugs which are commonly used for long-term immunotherapy of human patients were investigated. Hydrocortisone, prednisolone, cyclosporin A or azathioprine was administered daily for 7 consecutive days either topically by application to the skin, or systemically by intraperitoneal injection. LC densities were determined on the day following cessation of treatment by staining for the plasma membrane-bound enzyme adenosine triphosphatase (ATPase). All immunosuppressants caused a significant reduction in ATPase-positive LC when administered topically, but not systemically. The systemically administered drugs, although given in high concentration, may not have penetrated the epidermis in sufficient concentrations to disrupt the LC membrane. These observations are consistent with long term immunosuppressants depleting cutaneous LC by bone marrow suppression rather than by a direct effect on LC.

Adenosine Triphosphatases↗
PubMed2004

Levamisole in steroid-sensitive nephrotic syndrome children with frequent relapses and/or steroid dependency: comparison of daily and every-other-day usage.

Steroid dependency (SD) and frequent relapses (FR) are common with steroid-sensitive nephrotic syndrome (SSNS). We assessed the effectiveness of daily levamisole in 36 children with SSNS with FR and/or SD. Twenty patients (group 1) were given levamisole 2-3 mg/kg q.o.d. for 4-24 months. Sixteen (group 2) had relapses within 3 months: 5 received levamisole q.d. for 3-18 months, and 11 q.d. for 6 months and then q.o.d. for 4-18 months. Follow-up was 4-36 (mean 20.4 +/- 9.2) months. After therapy, relapses (4.82 +/- 3.15 vs. 2.01 +/- 2.5 in group 1; 5.97 +/- 3.38 vs. 1.34 +/- 2.1 in group 2; p < 0.05) and prednisolone doses (0.57 +/- 0.37 vs. 0.15 +/- 0.33 mg/kg/day in group 1; 0.61 +/- 0.42 vs. 0.19 +/- 0.35 mg/kg/day in group 2; p < 0.05) decreased. Relapse frequency, prednisolone dose, response percentage, and survival curves for remission did not differ between groups. Group 1 had five episodes of leukopenia, and group 2 had four. White blood cell counts normalized after levamisole was discontinued. Serum blood urea nitrogen/creatinine and alanine aminotransferase/aspartate aminotransferase levels were normal. Levamisole is effective in maintaining remission in children with SSNS and FR and/or SD. Daily levamisole can be considered when responses to q.o.d. usage are unsatisfactory.

Adolescent↗
PubMed1987

Steroid-sensitive mechanism of soluble immune response suppressor production in steroid-responsive nephrotic syndrome.

Soluble immune response suppressor (SIRS), a lymphokine that suppresses antibody production and delayed type hypersensitivity in vivo, has been detected in urine and serum from certain patients with nephrotic syndrome. In the present paper, the relationship between SIRS production and nephrotic syndrome is further characterized. A striking correlation was found between detection of SIRS and the presence of steroid-responsive nephrotic syndrome (SRNS). A potential mechanism of SIRS production in SRNS patients was identified, in that lymphocytes from patients produced SIRS without requiring activation by exogenous agents, and incubation of normal lymphocytes with serum from patients activated the cells to secrete SIRS in culture. Although SIRS disappears rapidly from urine or serum after initiation of corticosteroid therapy, hydrocortisone (10(-6)-10(-7) M) did not block secretion of SIRS by activated suppressor cells. It did, however, inhibit in vitro activation of lymphocytes to produce SIRS by concanavalin A, interferon, or SRNS patient serum. The association of suppressor cell activation with SRNS and the sensitivity of both to steroids suggest that the pathogeneses of albuminuria and SIRS production are related.

Antigen-Antibody Reactions↗
PubMedDate not supplied

An evaluation of total parenteral nutrition in the management of steroid-dependent and steroid-resistant patients with Crohn's disease.

This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes.

Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of androgenic-anabolic steroids, and during the 13 weeks following drug withdrawal. During the use of steroids significant decreases (P less than 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyroxine, triidothyronine, free thyroxine, and thyroid hormone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P less than 0.001). In relation to the changes in the thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hormone increased at some point of the study 5 to 60-fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P less than 0.001) in serum estradiol. Furthermore, there were major decreases in serum LH (P less than 0.01) and FSH (P less than 0.01) concentrations, and testicular testosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 +/- 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 +/- 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of testicular endocrine function. No consistent changes were found in the eight control athletes.

Adult↗
PubMedDate not supplied

Comparative evaluation of the short-term bactericidal potential of a steroid-antibiotic combination versus steroid in the treatment of chronic bacterial blepharitis and conjunctivitis.

The effects of four days' treatment with topical Maxitrol (neomycin sulphate 3500 IU/mL, polymyxin-B sulphate 6000 IU/mL with dexamethasone 0.1%) were compared with those of Maxidex (dexamethasone 0.1% alone) in a double-masked study in 111 patients with bacterial blepharitis or conjunctivitis, 95 of whom were evaluable for efficacy. The majority of patients (N = 80) had chronic blepharitis. Maxitrol treatment resulted in a significantly greater reduction (90%) in bacterial counts and bacterial eradication (50%) compared with Maxidex (34% and 17% respectively). Maxitrol treatment also produced a significantly greater reduction in conjunctival discharge than did Maxidex, while the treatments were equally effective in alleviating other ocular signs and symptoms. It was concluded that use of a fixed dose combination steroid-antibiotic product was more effective for bacterial control and therapeutic efficacy in the treatment of chronic blepharitis and conjunctivitis patients than treatment with steroid alone. However, in the long-term treatment of chronic blepharitis the well-known toxic problems of neomycin sulphate have to be taken into account.

Administration, Topical↗
PubMed1991

Presence of identical mitochondrial proteins in unstimulated constitutive steroid-producing R2C rat Leydig tumor and stimulated nonconstitutive steroid-producing MA-10 mouse Leydig tumor cells.

The acute regulation of steroidogenesis in steroidogenic tissues requires de novo protein synthesis. It is believed that these newly synthesized proteins are instrumental in the delivery of the substrate, cholesterol, to the inner mitochondrial membrane where the cholesterol side-chain cleavage complex converts cholesterol to pregnenolone. A number of studies have attempted to characterize the protein(s) synthesized in response to hormone stimulation and, hence, function in the delivery of cholesterol to the cholesterol side-chain cleavage complex. While a number of potential protein candidates have been described, there is at present no unequivocal evidence which indicates that they are involved in steroidogenic regulation. We and others have described proteins that are induced in a variety of steroidogenic tissues in response to hormone stimulation and are localized in the mitochondria of these tissues. In an attempt to determine whether these induced proteins may be involved in steroidogenesis, we compared mitochondrial protein profiles in two separate Leydig tumor cell line. One cell line, the MA-10 mouse Leydig tumor cell line, has a very low basal steroid production, but synthesizes large amounts of progesterone in response to both tropic hormone and cAMP analog. The other cell line, the R2C rat Leydig tumor cell line, produces constitutively large amounts of progesterone, which cannot be increased further with hormone stimulation. Two-dimensional polyacrylamide gel electrophoresis profiles of newly synthesized mitochondrial proteins demonstrated that four 30-kDa proteins are induced in response to hormonal stimulation in MA-10 cells. Further, it was shown that proteins identical to these induced proteins are present constitutively in the mitochondria of R2C cells and cannot be further increased with hormone stimulation. These results strongly suggest that the 30-kDa mitochondrial proteins shown to be induced in several steroidogenic tissues are involved in the acute regulation of steroid production.

Animals↗
PubMed1975

Adrenal and ovarian steroid secretion in the rat estrous cycle temporally related to gonadotropins and steroid levels found in peripheral plasma.

This study was undertaken to determine the patterns of estrogen and progestin secretion by the adrenal and the ovary and to relate these to the levels of steroids and gonadotropins found in peripheral plasma. A total of 70 rats were used in this study. Adrenal venous (ADVB) and ovarian venous blood (OVB) were collected by concurrent cannulation and peripheral blood (PB) was obtained from the abdominal aorta. Estrone (E1), estradiol (E2), PROGESTERONE (P) and 17alpha-hydroxyprogesterone (17alpha-OHP) were measured by radioimmunoassay. The concentration of E2 in general was higher in ADVB than in OVB. Although increased levels of E2 in ADVB were found on the afternoon of proestrus (1527-2634 pg/ml), they were not significantly different from those recorded at other times. In contrast E2 in OVB was lowest at 1000-1200 hr of estrus (225 pg/ml) and highest at 1000-2000 hr of proestrus (1190-1605 pg/ml). The E2 in PB followed the pattern seen in OVB; the values ranged from 80-211 pg/ml. P concentration in general was higher in ADVB than in OVB. The lowest concentration of P in ADVB was between 0200-0400 hr of estrus (183 ng/ml) and the highest between 1400-1600 hr of proestrus (580 ng/ml) and 1000-1200 hr of estrus (591 ng/ml). The lowest concentration of P in the OVB was between 1600-1800 hr of diestrus (42 ng/ml) and the highest between 0200-0400 hr of estrus (466 ng/ml). In the PB, P reflected changes in adrenal as well as ovarian secretion; the values ranged fron 7-25 ng/ml. E1 in ADVB was in general lower than in OVB, and there were no significant changes at any stage of the cycle. In the OVB, however, E1 showed a pattern similar to that of E2. Levels of E1 in PB were very low and failed to show any significant changes. 17alpha-OHP was high in ADVB, although there were no significant changes during the cycle; PB levels also did not show any significant changes. In the OVB a peak of 17alpha-OHP was recorded between 0200-0400 hr on the day of estrus. The LH and FSH levels showed increases after 1600 hr on the day of proestrus and this was in agreement with earlier studies. Since the adrenal secretes all of the 4 steroids studied, it is reasonable to assume that it does exert some effect in the pituitary-gonadal axis. A role of adrenal P for the facilitation of the preovulatory LH release has been indicated and the increased secretion of adrenal P between 1400-1600 hr of proestrus supports this possibility.

Adrenal Glands↗
PubMed1993

Effect of combination treatment with zanoterone (WIN 49596), a steroidal androgen receptor antagonist, and finasteride (MK-906), a steroidal 5 alpha-reductase inhibitor, on the prostate and testes of beagle dogs.

The effects of the steroidal androgen receptor antagonist zanoterone (WIN 49596) and the steroidal 5 alpha-reductase inhibitor finasteride (MK-906) either alone or in combination on prostatic size, histomorphology, and biochemistry were determined in the intact male dog. Additionally, the effects of treatment with zanoterone and/or finasteride on testicular size, serum testosterone and LH levels, and spermatogenesis were determined in the same dogs. Daily oral treatment for 16 weeks with either zanoterone alone at 10 mg/kg.day or finasteride alone at 1.0 mg/kg.day reduced (P < 0.05) the size of the prostate, resulted in mild to moderate diffuse glandular atrophy of the prostate, and decreased prostatic DNA and prostatic arginine esterase (the primary canine prostatic protein) levels compared to those in intact controls. These changes occurred with no effect on testicular weight, testicular histomorphology, daily sperm production, or serum LH levels. Serum testosterone concentrations were increased (P < 0.05) approximately 3-fold in the 10 mg/kg.day zanoterone treatment group compared to those in intact controls. Combination treatment of male dogs for 16 weeks with zanoterone (10 mg/kg.day) plus finasteride (1.0 mg/kg.day) orally also reduced (P < 0.05) prostate size, resulted in moderate to marked diffuse prostatic glandular atrophy, and decreased prostatic DNA and arginine esterase levels more than either drug alone, without affecting testicular size, testicular histomorphology, serum LH concentrations, or serum testosterone concentrations compared to those in intact controls. The effects of combination treatment with zanoterone and finasteride on prostatic size; histomorphology; and DNA, arginine esterase protein, and arginine esterase mRNA levels were similar to those observed in castrate controls. In addition, in situ estimates of prostatic size using transrectal ultrasonography indicated that the median time to 70% prostatic regression in dogs administered combination zanoterone plus finasteride was similar to that in castrate controls (9.6 and 9.3 weeks, respectively), indicating that the combination was more effective in causing prostatic regression than either drug alone. Finally, at the dosages used, no adverse effects of combination treatment with zanoterone plus finasteride on testicular or other major body organ weights were observed. Based on these results, combination therapy using zanoterone and finasteride for the treatment of human androgen-dependent disorders such as benign prostatic hyperplasia and prostate cancer has potential utility.

Androstenes↗
PubMed1993

Effects of steroid and lactogenic hormones on islets of Langerhans: a new hypothesis for the role of pregnancy steroids in the adaptation of islets to pregnancy.

Adaptive changes that occur in islets of Langerhans during pregnancy include enhanced insulin secretion, insulin synthesis, beta-cell proliferation, gap-junctional coupling among beta-cells, and glucose oxidation. We have determined that elevated lactogenic activity is directly responsible for these changes in beta-cell function. Recently, we showed that two of the principal adaptive characteristics (insulin secretion and beta-cell proliferation) of rat pregnancy peaked on day 15 and returned to control levels by day 20. As placental lactogen remains elevated during late gestation, it was of interest to determine whether pregnancy steroids could reverse the effects of lactogen on islets. In this study, rat islets were cultured with progesterone, estradiol, rat PRL (rPRL), or combinations of these hormones (progesterone and rPRL, estradiol and rPRL, or progesterone and estradiol and rPRL). Insulin secretion was examined for 8 days, and beta-cell proliferation by 2-bromo-5'-deoxyuridine (BrdU) incorporation on days 4 and 8. rPRL treatment resulted in a time-dependent increase in insulin secretion that was 3-fold greater than that from control islets by day 8. Progesterone and estradiol had minimal effects on insulin secretion. Estradiol had no effect on the increased insulin secretion observed with rPRL during the first 6 days and a small inhibitory effect on days 7 and 8. Although progesterone treatment had no effect on the increased insulin secretion induced by rPRL during the first 3 days, it subsequently resulted in a decline in insulin secretion to that from control islets. The combination of progesterone and estradiol was more effective than either steroid by itself in reversing the effects of rPRL on insulin secretion. Similar results were obtained in the BrdU labeling experiments: 1) a 7-fold increase in the number of BrdU-labeled nuclei per islet was observed after culture in the presence of rPRL; and 2) estradiol had a small inhibitory effect on the increased BrdU labeling observed with rPRL; however, 3) progesterone completely reversed the effect of rPRL on islet beta-cell division. These results demonstrate that progesterone counterregulates the effects of PRL on insulin secretion and islet beta-cell division. The temporal changes observed in islets in vitro under the influence of PRL and progesterone mimic those seen in islets during pregnancy. We conclude that progesterone, which increases in the later stages of gestation, is the primary hormone responsible for counteracting the stimulatory effects of elevated lactogenic activity on islets during late pregnancy.

Animals↗
PubMed1997

The interaction between beta-endorphin and gonadal steroids in regulation of luteinizing hormone (LH) secretion and sex steroid regulation of LH and proopiomelanocortin peptide secretion by individual pituitary cells.

Reported studies using the conventional pituitary cell culture technique suggest that beta-endorphin (B-EP) produced locally in the pituitary or reaching it from the hypothalamus acts in conjunction with estradiol (E2) to initiate and in conjunction with progesterone (P4) to terminate the midcycle surge of LH. In addition, the reverse hemolytic plaque assay (RHPA) was used to investigate the effects of E2 and P4 on the secretory activity of individual pituitary cells. The results of these experiments indicate that 1) E2 enhances the secretion of LH, ACTH, and B-EP by individual pituitary cells; 2) E2 increases the number of secreting cells for each of the three hormones; 3) the rise in B-EP and ACTH secretion antecede that of LH; 4) P4 augments ACTH and B-EP secretion by individual pituitary cells; and 5) P4 has dual effects, acutely (1 h) potentiating LH secretion from already active cells and subsequently (8 h) recruiting cells that formerly had little or no secretory activities. Collectively, the above studies support a role for steroid hormones in regulation of midcycle LH secretion at the pituitary level. The results also suggest that intrapituitary (paracrine/autocrine) and extrapituitary (endocrine) B-EP modulates gonadal steroid effects on LH secretion by pituitary gonadotrophs.

Adrenocorticotropic Hormone↗
PubMed1983

Control of plasma sex steroid-binding protein in the bat Myotis lucifugus lucifugus: induction of steroid-binding activity in immature males.

Concentrations of sex steroid-binding protein (SBP) in plasma of immature male little brown bats (Myotis lucifugus lucifugus) were found to be low (15 +/- 2.8 (S.E.M) nmol/l) and stable throughout the period of hibernation which immediately precedes the onset of the first spermatogenic cycle (sexual maturity). In contrast, plasma SBP titres in spermatogenically active adults (summer) were markedly raised (238 +/- 26 nmol/l). When immature males were removed from hibernation and maintained on a long photoperiod of 16 h light: 8 h darkness at a constant temperature of 25 degrees C to accelerate the onset of sexual maturity, these animals exhibited a rapid rise in circulating SBP. Plasma levels of SBP in immature males maintained on a long photoperiod increased significantly after 2 weeks, and by 3 weeks reached values (234 +/- 20 nmol/l) that were indistinguishable from those seen in spermatogenically active adults. These high plasma SBP titres at 3 weeks were accompanied by increases in testicular and epididymal weights and the onset of spermatogenesis. However, no stimulation of the sex accessory glands was observed, possibly reflecting the effects of increased plasma SBP on the biological activity of circulating androgens. The ability of immature male Myotis to exhibit a pubertal increase in plasma SBP following simple environmental manipulation should provide a valuable model for the study of the control and action of sex steroid-binding protein.

Animals↗
PubMed2006

Tissue-specific transcriptional initiation and activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue.

Expression analysis by reverse transcriptase (RT)-PCR indicates that human adipose tissue is not likely to perform de novo synthesis of steroid hormones from cholesterol because the mRNAs of cytochromes P450scc and P450c17, and of the steroidogenic-related proteins, steroidogenic acute regulatory protein and steroidogenic factor 1, were not detected. Instead, our data support an intracrine role of adipose tissue, in which adrenal dehydroepiandrosterone sulfate (DHEA-S), the most abundant circulating androgen in man, is selectively uptaken, desulfated, and converted into bioactive androgens and estrogens. Three organic anion-transporting polypeptides-B, -D, and -E, presumably involved in DHEA-S transmembrane transport, were demonstrated at the mRNA level. While sulfotransferase expression was not found, the occurrence of steroid sulfatase (STS), converting DHEA-S to DHEA, was established at the mRNA, protein and catalytic activity levels. The 5'-rapid amplification of cDNA ends analysis showed that STS transcription in adipose tissue is regulated by the use of two promoters which differ from the prevalent placental one. The adipose transcripts contain a distinct untranslated first exon, 0a or 0b, followed by a common partially translated exon 1b, and nine other exons that are also shared by the main placental transcript. The presence of an upstream open reading frame in the new transcript variants could lead to an N-terminal divergence restricted to the cleavable signal peptide and thus not interfering with the catalytic activity of the mature STS protein. The adipose transcripts are also present in the placenta as minor isoforms. Western blotting revealed the characteristic approximately 64 kDa band of STS in both the placenta and adipose tissue. The specific enzymatic activity of STS in adipocytes was 118 pmol/10(6) cells per hour, about 50-100 times lower than in the placenta. A similar rate of [3H] DHEA-S uptake plus desulfation was measured in preadipocytes and adipocytes, equivalent to 40-45 pmol/10(6) cells per hour. Thus, an excessive accumulation of fat may out-compete other peripheral organs that are also dependent on intracrine DHEA-S utilization, especially when the adrenal production is low or declining with aging.

3' Untranslated Regions↗