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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-adrenergic receptor, transduction processes and catalytic activity of the adenylate cyclase enzyme complex have been investigated in rabbit heart at different stages of biological maturation. The binding of [3H]-dihydroalprenolol to a washed membrane preparation isolated from rabbit ventricular muscle was used to characterize beta-adrenergic receptors. Significant age-related differences were noted in beta-receptor affinity (Kd) and density (RD) of neonatal and adult animals; the adult Kd was 3.7-fold greater and the RD 2-fold higher than the neonates. No significant differences in these parameters were detected among the 27-day old fetus and the 1- and 7-day old neonates. Age-dependent differences in agonist isoproterenol affinity for the receptor were not observed in contrast to the significant changes in antagonist (DHA) affinity. Age-related changes in receptor affinity were also quantitated by determining the inhibitory potency of alprenolol on isoproterenol stimulated adenylate cyclase enzyme activity. A decreased affinity of the beta-adrenergic receptor for alprenolol in the adult heart was indicated by a 3.7-fold greater Ki for the adult than the 1-day old neonate. Ontogenic variations in the coupling efficiency between the receptor and catalytic components of the adenylate cyclase complex were also evaluated. The Kd of the beta-adrenergic receptor for isoproterenol and the EC50 for adenylate cyclase stimulation were determined under similar conditions. The corresponding coupling index (Kd/EC50) was found to be 2.4-fold greater in the 1-day old neonate than adult, suggesting that for a given percentage increase in adenylate cyclase activity, a lower percentage of beta-adrenergic receptor sites need be occupied in the neonate.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1984
PMID:Biological maturation and beta-adrenergic effectors: development of beta-adrenergic receptors in rabbit heart. 632 58

The mechanism by which GnRH acts on ovarian interstitial cells to inhibit androgen synthesis was studied in primary cultures of ovarian cells from hypophysectomized immature rats. Interstitial cells cultured in defined medium with LH showed a 200-fold increase in steroid production, of which androsterone was the principal metabolite (88% of the total steroid content). Treatment with GnRH (10(-8) M) inhibited LH-stimulated androsterone production by 92%. This inhibitory effect of GnRH was not due to changes in cell number, cell viability, or 125-I-hCG binding capacity. Prostaglandin E2, cholera toxin and 8-Br-cyclic AMP mimicked the LH effect on androsterone synthesis and these increases were also inhibited by GnRH. Metabolic studies of GnRH-treated cultures revealed that LH-stimulated androsterone and 5 alpha-androstane-3 alpha, 17 beta-diol were decreased by 90%; androstenedione, testosterone and DHEA were decreased by 70%; 17 alpha-hydroxypregnenolone and 17 alpha-hydroxyprogesterone were decreased by 50%; pregnenolone was unchanged; and progesterone was increased 40%. Collectively, these results suggest that GnRH directly inhibits androgen synthesis in ovarian interstitial cells by selectively inhibiting the 17 alpha-hydroxylase and C17-20 desmolase activities.
Mol Cell Endocrinol 1982 Jul
PMID:Mechanism by which GnRH inhibits androgen synthesis directly in ovarian interstitial cells. 674 79

Dehydroepiandrosterone sulphate (DHEAS) is a major adrenal secretory product, particularly in the fetus where it serves as a substrate for oestrogen biosynthesis by the placenta. The enzyme in the adrenal responsible for synthesising DHEAS, hydroxysteroid sulphotransferase (HST), is therefore essential for human development. We have isolated a full-length cDNA clone, encoding human fetal adrenal HST, and constructed a stable cell line expressing it by transfection into V79 Chinese hamster lung fibroblast cells. This cDNA was essentially identical to that isolated from adult human liver, where the role of HST is less well understood. This recombinant cell line allowed determination of the substrate specificity and kinetic properties of this enzyme towards various steroid hormones, and by comparison of these activities with human liver cytosol we have shown that HST is the major sulphotransferase responsible for the sulphation of DHEA, androsterone and pregnenolone in man and that, functionally, the hepatic and adrenal enzymes are very similar. The expressed HST was also active with testosterone, cortisol (although at low levels) and the xenobiotic 17 alpha-ethinyloestradiol, but not with oestrone or 1-naphthol. We have therefore created a valuable resource for the study of this important enzyme.
Mol Cell Endocrinol 1995 Jul
PMID:Human fetal adrenal hydroxysteroid sulphotransferase: cDNA cloning, stable expression in V79 cells and functional characterisation of the expressed enzyme. 758 85

To clarify the possible action of adrenal androgen on bone cell, the existence, characteristics and regulation of aromatase in human osteoblast-like osteosarcoma cells (HOS) and primary cultured osteoblast-like cells from normal human bones (HO) were examined in this study. Significant positive correlation between bone mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51-99 years old) but no correlation was seen between BMD and serum estradiol (E2). In subset analysis, strongly positive correlation of serum DHEA-S and estrone (E1) with BMD was observed in postmenopausal women aged less than 69 years old. Administration of DHEA to ovariectomized rat significantly increased BMD and decreased relative osteoid volume in femur. These in vivo findings strongly suggested that serum adrenal androgen may be converted to estrogen in peripheral organ, especially, osteoblast and be important steroids to maintain BMD. [3H]DHEA was converted to [3H]androstenedione and [3H]androstenedione to [3H]estrone in primary cultured human osteoblast. Osteoblast-like cells showed aromatase activity, and an apparent Km and the Vmax were 4.74 +/- 0.78 nM (mean +/- SD, n = 3) and 0.83 +/- 0.79 fmol/mg protein/h for HOS, and 4.6 +/- 2.9 nM and 279 +/- 299 fmol/mg protein/h (mean +/- SD, n = 19) for HO, respectively. The aromatase activity was significantly increased by dexamethasone in a dose-dependent manner. Reverse transcription-polymerase chain reaction analysis revealed that dexamethasone increased the transcript of P450AROM gene. Osteoblast-specific promoters were also determined. Dexamethasone and 1 alpha,25-dihydroxyvitamin D3 synergistically enhanced aromatase activity and P450AROM mRNA expression. These results demonstrate that adrenal androgen, DHEA, is converted to E1 in osteoblast by P450AROM which is positively regulated by glucocorticoid and 1 alpha,25-dihydroxyvitamin D3 and important to maintain BMD in the 6 to 7th decade, after menopause.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Aromatase in bone cell: association with osteoporosis in postmenopausal women. 762 49

Pregnenolone (PREG), synthesized de novo in rodent brain, is the precursor of PREG sulfate (S) and progesterone (PROG). PROG is further converted to 5 alpha-pregnane 3, 20-dione (DH PROG) and to 3 alpha-hydroxy-5 alpha-pregnan-20-one (TH PROG). PROG, DH PROG and TH PROG have been measured in the brain of male and female rats. Neither PROG nor DH PROG disappeared from brain, contrary to plasma, after combined adrenalectomy (ADX) and gonadectomy (CX). Trilostane decreased PROG and increased PREG in the brain of CX+ADX rats and mice, in accordance with a precursor to product relationship. As previously described in CX male mice, the neurosteroid DHEA and its analog 3 beta-methyl-androst-5-en-17-one (CH3-DHEA) inhibited the aggressive behavior of female mice towards lactating female intruders. The decrease of biting attacks by DHEA was definitely more prominent in females neonatally imprinted with testosterone. The degree of inhibition of aggressive behavior was related to the decrease of PREG S concentrations in brain. The memory-enhancing effects of DHEA S and PREG S in male mice have been previously documented. Infusion of PREG S (12 fmol) into the nucleus basalis magnocellularis (NBM) of the rat after the acquisition trial enhanced memory performance in a two-trial recognition task (TTRT). Conversely, TH PROG (6 fmol), which potentiates GABAergic neurotransmission, disrupted performance when injected before the acquisition trial. Accordingly, we have found a positive correlation between the performances of 2-year-old rats in the TTRT and the concentrations of PREG S in the hippocampus, namely animals which performed best had the highest steroid levels.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Biosynthesis and assay of neurosteroids in rats and mice: functional correlates. 762 80

Estrone sulphate (E1S) may be an important estrogen source in breast cancers, particularly in postmenopausal women. Recent studies have shown that tamoxifen inhibits the uptake and metabolism of E1S to estradiol (E2) in cell cultures. To evaluate a possible influence of tamoxifen on E1S disposition in vivo, we measured plasma levels of E1S together with unconjugated estrogens (E1 and E2), androgens (T, A, DHEA and DHEAS), SHBG, FSH and LH in 32 postmenopausal breast cancer patients before and during tamoxifen treatment. In a subgroup of 10 patients, we measured 24 h urinary excretion of estrogen metabolites to evaluate the influence of tamoxifen treatment on estrogen metabolism and total estrogen production. Tamoxifen increased plasma levels of E1S (mean increase of 18.1%, P < 0.05) and the ratio of E1S/E1 (mean increase of 25.7%, P < 0.01) and E1S/E2 (mean increase of 34.7%, P < 0.0005). No significant change in plasma E1 was seen, but plasma E2 was reduced (mean reduction of 12.1%, P < 0.005). The fall in plasma E2 was probably secondary to a fall in plasma T (mean reduction of 11.9%, P < 0.05) due to a reduced ovarian excretion of this androgen. The mechanisms may be a reduced gonadotrophin stimulation of the ovary, as plasma FSH and LH fell by mean values of 45.5 and 48.1%, respectively (P < 0.0001 for both). The increase in plasma E1S was accompanied by a reduced ratio of 2OHE1/E1 in urine (mean reduction of 38.2%, P < 0.025) indicating reduced 2-hydroxylation. Possible mechanisms for these alterations are discussed.
J Steroid Biochem Mol Biol 1995 May
PMID:Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. 774 14

It is well established that DHEA treatment is associated in the rat to an increase in fatty acids metabolism. This condition would require levels of L-carnitine much higher than those physiologically present in the liver. The possibility thus exist that during DHEA treatment the concentration of L-carnitine may become a limiting factor for fatty acids oxidation and therefore responsible of some of the effects observed after administration of the hormone. The present experiments were designed to test this hypothesis. The results show that the increase in the levels of peroxisomal enzymes induced in hepatocytes by DHEA, is greatly reduced by parallel administration of L-carnitine. Furthermore, L-carnitine administration counteracts the effect of DHEA on mitochondrial structure. On the contrary, carnitine has no significant effect on the reduction in weight gain observed upon short- or long-term treatment with DHEA.
Biochem Mol Biol Int 1994 Aug
PMID:Effects of dehydroepiandrosterone and carnitine treatment on rat liver. 780 31

Dehydroepiandrosterone-sulfate (DHEA-S), the main secretory product of the human adrenal, requires the presence of steroid sulfatase, 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), 5 alpha-reductase, and aromatase to form the active androgen dihydrotestosterone (DHT) and the estrogens 17 beta-estradiol (E2) and 5-androst-ene-3 beta,17 beta-diol (delta 5-diol) in peripheral target tissues. Because humans, along with non-human primates are unique in having adrenals that secrete large amounts of DHEA-S, the present study investigated the tissue distribution of the enzymatic activity of the above-mentioned steroidogenic enzymes required for the formation of active sex steroids in the male and female rhesus monkey. Estrone and DHEA sulfatase activities were measured in all 25 tissues examined, and with the exception of the salivary glands, estrogenic and androgenic 17 beta-HSDs were present in all the tissues examined. The adrenal, small and large intestine, kidney, liver, lung, fat, testis, prostate, seminal vesicle, ovary, myometrium, and endometrium all possess the above-mentioned enzymatic activities, thus suggesting that these tissues could possibly form the biologically active steroids E2 and DHT from the adrenal precursor DHEA-S. On the other hand, the oviduct, cervix, mammary gland, heart, and skeletal muscle possess all the enzymatic activities required to synthesize E2 from DHEA-S. The present study describes the widespread tissue distribution of steroid sulfatase, 3 beta-HSD, 17 beta-HSD, 5 alpha-reductase, and aromatase activities in rhesus monkey peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Aug
PMID:Widespread tissue distribution of steroid sulfatase, 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD), 17 beta-HSD 5 alpha-reductase and aromatase activities in the rhesus monkey. 782 1

beta-Adrenoreceptor has been studied in a clonal capillary endothelial cell line established from the vascular bed of the bovine adrenal medulla. [3H]Dihydroalprenolol ([3H]DHA) binding to the isolated plasma membranes from these cells has demonstrated the presence of beta-adrenoreceptors with two different affinities. The dissociation constants (Kd) have been found to be 0.27 +/- 0.09 x 10(-9) M and 2.96 +/- 0.31 x 10(-9) M, respectively with the corresponding Bmax of 5.1 +/- 0.05 and 70.0 +/- 0.2 pmol/mg protein, respectively. Inhibition of [3H]DHA binding to the beta-receptor by atenolol (a beta 1-antagonist) and ICI 118,551 (a beta 2-antagonist) has suggested that the IC50cor (= Ki) for atenolol and ICI 118,551 for high affinity site are 0.08 +/- 0.03 x 10(-12) M and 0.25 +/- 0.08 x 10(-12) M, respectively. This, therefore, indicates that both atenolol and ICI 118,551 are able to displace the bound ligand effectively but the beta 1-selective antagonist atenolol is 3 times more potent than its beta 2 counterpart, ICI 118,551. Displacement of [3H]DHA binding to the endothelial cell plasma membrane by the agonists isoproterenol, epinephrine and norepinephrine has established a relative order of Ki for these agents as isoproterenol (0.56 +/- 0.19 x 10(-9) M) < epinephrine (0.77 +/- 0.26(-9) M) > or = norepinephrine (0.71 +/- 0.24 x 10(-9) M) for the high affinity site. The corresponding values for the low affinity site, however, are 4.62 +/- 0.64 x 10(-9) M, 6.21 +/- 0.86 x 10(-9) M and 5.90 +/- 0.82 x 10(-9) M, respectively for the same agonists. Increased intracellular cAMP accompanied with cellular proliferation in the presence of isoproterenol has suggested not only the coupling of beta-adrenoreceptors to the adenylate cyclase system but also its involvement in endothelial cell proliferation.
Mol Cell Biochem 1994 Nov 09
PMID:Beta-adrenoreceptors of multiple affinities in a clonal capillary endothelial cell line and its functional implication. 787 97

Whether the same or distinct steroid sulphatases (STS) are involved in the hydrolysis of alkyl and aryl steroid sulphates remains controversial. We have examined the ability of a placental steroid sulphatase to hydrolyse oestrone sulphate and/or dehydroepiandrosterone sulphate (DHA-S) by expressing the enzyme in COS-1 cells. Using either intact cells or broken cell preparations, the expressed sulphatase was found to hydrolyse both oestrone sulphate and DHA-S. The catalysis of oestrone sulphate and DHA-S by the expressed sulphatase was almost completely abolished by the steroid sulphatase inhibitor, oestrone-3-O-sulphamate. It is concluded that both alkyl and aryl steroid sulphates can be hydrolysed by the same steroid sulphatase.
J Steroid Biochem Mol Biol 1994 Jul
PMID:The hydrolysis of oestrone sulphate and dehydroepiandrosterone sulphate by human steroid sulphatase expressed in transfected COS-1 cells. 804 27


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