Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The AMP-activated protein kinase (AMPK) is a major regulator of energy metabolism involved in fatty acid and cholesterol synthesis. In the ovary, cholesterol plays a key role in steroid production. We report the presence of AMPK in rat ovaries, and we have investigated its role in granulosa cells. We show using RT-PCR and Western blot that the mRNAs for the alpha1/2 and beta1/2 subunits and the proteins are found in the ovaries. Immunohistochemistry localized the alpha1 AMPK subunit in granulosa cells, corpus luteum, and oocyte and less abundantly in theca cells. Treatment with 1 mm 5-amino-imidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR), an activator of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPKalpha1 on Thr172 in primary granulosa cells. Simultaneously, phosphorylation of acetyl-coenzyme A carboxylase at Ser79 was also increased. AICAR treatment for 48 h halved progesterone secretion, 3beta-HSD protein and mRNA levels, and phosphorylation of both basal MAPK ERK1/2 and p38 and in response to IGF-I and/or FSH in granulosa cells. AICAR treatment (1 mM) had no detectable effect on basal and FSH- and/or IGF-I-induced estradiol production and on granulosa cell proliferation or viability. Adenovirus-mediated expression of dominant negative AMPK totally abolished the effects of AICAR on progesterone secretion, 3beta-HSD protein production, and MAPK ERK1/2 and p38 phosphorylation. Moreover, we showed using specific in- hibitors of ERK1/2 and p38 MAPK that the MAPK ERK1/2 and not p38 is involved in progesterone secretion and 3beta-HSD expression, strongly suggesting that the activation of AMPK in response to AICAR reduces progesterone production through the MAPK ERK1/2 signaling pathway in rat granulosa cells.
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PMID:Adenosine 5'-monophosphate-activated protein kinase regulates progesterone secretion in rat granulosa cells. 1602 Apr 77

Menopause state doesn't mean total ovarian failure. Function of stromal cells is maintained and steroids, especially androgens, are produced. The role of androgenesis after menopause is important because of general androgens activity and their influence on some symptoms characteristic for perimenopausal period. From the other side, these hormones are necessary for the proper quality of life connected with bone mass density, libido, mood and physical activity. Knowledge of postmenopausal ovarian androgenesis and its influence on total androgens level is still not completed. On the basis of result of immunohistochemical assays it was found, that T and A postmenopausal production is depended on: hyperplasia of stromal tissue, receptors of Gn-FSH and Gn-LH, steroids receptors: ER, PR and AR, enzymes: P-140 aromatase, 3-beta HSD, 17-beta HSD activity. But influence the estrogen replacement therapy on these factors is still unknown.
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PMID:[Ovarian androgenesis in women after menopause]. 1619 37

We repeatedly established a nontransformed steroidogenically active human ovarian cell culture derived from oophorectomy specimens. The cells maintained steroidogenic activity for 3-5 passages (6-8 weeks) and responded to stimulation by insulin and gonadotropin. With pregnenolone as substrate, LH stimulated progesterone production up to 124% and FSH up to 121%. Insulin alone stimulated progesterone production up to 135%, in the presence of LH up to 191%, and in the presence of FSH up to 170%. With dehydroisoandrosterone (DHA) as substrate, insulin alone stimulated testosterone production up to 117%, and in the presence of LH (but not FSH) up to 125%. With androstenedione as substrate, insulin alone stimulated estradiol production up to 133%, FSH alone up to 188%, and LH with insulin up to 217%. With progesterone as substrate and in the presence of LH (but not FSH), 17-alpha-hydroxylase activity was stimulated up to 131%. With DHA as substrate and in the presence of LH, 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) activity was stimulated up to 139%. With androstenedione as substrate, insulin alone stimulated aromatase activity up to 202%, LH up to 208%, and FSH up to 251%. Under the same conditions, in the presence of LH and insulin, aromatase activity was stimulated up to 342%, and in the presence of FSH and insulin, up to 318%. With testosterone as substrate, insulin alone stimulated aromatase activity up to 122%. With testosterone as substrate, in the presence of LH and insulin, aromatase activity was stimulated up to 136%, and in the presence of FSH and insulin, up to 156%. Immunocytochemistry studies directly confirmed presence of aromatase and 3-beta-HSD in these cultured cells. We conclude that a steroidogenically active nontransformed long-term human ovarian cell culture can be repeatedly established from oophorectomy specimens, providing uninterrupted supply of cultured human ovarian cells for a variety of studies of ovarian physiology.
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PMID:Hormonally active nontransformed human ovarian cell culture from oophorectomy specimens: methods of development and initial characterization. 1626 Aug 96

Exposure of neonatal testis, populated by fetal-type Leydig cells, to endocrine-active compounds may have far-reaching consequences. Our aim was to resolve the sensitivity of testosterone synthesis of infant rat (Sprague-Dawley) testis to diethylstilbestrol (DES; 0.1-1.0 mg/kg), 4-tert-octylphenol (OP; 10-100 mg/kg), and Flutamide (FLU; 2.0-25 mg/kg) given by daily sc injections from birth to postnatal day 4. Testes and serum were collected on day 14 when body and testis weight, testicular histology, circulating testosterone, LH and FSH levels, and steroidogenic acute regulatory protein (StAR) and 3beta-hydroxy-steroid-dehydrogenase (3beta-HSD) protein levels were determined. DES at each dose and FLU at 25 mg/kg dose reduced testis weight and the diameter of seminiferous cords. FLU caused some Leydig cell hyperplasia. Plasma testosterone was reduced in all DES animals, LH elevated in DES 0.5 mg/kg and FLU 25 mg/kg animals, and FSH reduced in the DES 1.0 mg/kg group. Basal testicular ex vivo progesterone and human chorionic gonadotropin (hCG)-stimulated testosterone production were decreased in DES animals. Despite a decrease in hCG-induced cyclic adenosine-3',5'-monophosphate (cAMP) production, intratesticular testosterone was increased in the FLU 10 and 25 mg/kg groups. OP 100 mg/kg elevated hCG-induced progesterone production only. No changes were seen in 3beta-HSD protein levels in any treatment group. StAR levels were reduced in DES animals. The results indicate the sensitivity of postnatal fetal-type Leydig cells to endocrine-active compounds. Suppression of StAR expression level was an early sign of the DES-induced steroidogenic lesion. FLU-induced changes suggest the importance of androgen receptor-mediated regulation of testosterone synthesis in the postnatal rat testis. Octylphenol appeared less effective in bringing about acute steroidogenic changes.
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PMID:Effects of neonatal exposure to 4-tert-octylphenol, diethylstilbestrol, and flutamide on steroidogenesis in infantile rat testis. 1653 57

We investigated the effects of theca cells or FSH on granulosa cell differentiation and steroid production during bovine early follicular growth, using a co-culture system in which granulosa and theca cells were cultured on opposite sides of a collagen membrane. Follicular cells were isolated from early antral follicles (2-4 mm) that were assumed to be in gonadotropin-independent phase and just before recruitment into a follicular wave. Granulosa cells were cultured under serum-free conditions with and without theca cells or recombinant human FSH to test their effects on granulosa cell differentiation. Messenger RNA levels for P450 aromatase (aromatase), P450 cholesterol side chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), LH receptor (LHr), and steroidogenic acute regulatory protein (StAR) in granulosa cells were measured by real-time quantitative RT-PCR analysis. FSH enhanced aromatase mRNA expression in granulosa cells, but did not alter estradiol production. FSH also enhanced mRNA expression for P450scc, LHr, and StAR in granulosa cells, resulting in an increase in progesterone production. In contrast, theca cells enhanced aromatase mRNA expression in granulosa cells resulting in an increase in estradiol production. Theca cells did not alter progesterone production and mRNA expression in granulosa cells for P450scc, 3beta-HSD, LHr, and StAR. The results of the present study indicate that theca cells are involved in both rate-limiting steps in estrogen production, i.e., androgen substrate production and aromatase regulation, and that theca cell-derived factors regulate estradiol and progesterone production in a way that reflects steroidogenesis during the follicular phase of the estrous cycle.
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PMID:Effects of ovarian theca cells on granulosa cell differentiation during gonadotropin-independent follicular growth in cattle. 1654 62

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide have long been considered as putative regulators of testicular functions. In vitro evidence suggests that VIP could play an important role in testosterone biosynthesis. However, the endogenous role of VIP on testicular functions remained to be demonstrated. In C57BL/6 mice exhibiting a complete disruption of the VIP gene, we first observed here that serum testosterone levels were lower than those of WT littermates. At the age of 4 months, this phenotype was accompanied with a reduction of expression of StAR and 3-beta-hydroxysteroid dehydrogenase (3beta-HSD) in the testis. In addition, serum levels of FSH but not LH were reduced in young knock-out (KO) males. Testicular anatomy also revealed a higher percentage of degenerated seminiferous tubules in the 4-month-old VIP KO animals when compared with WT. In 15-month-old animals, control males showed typical testicular aging, including a severe degeneration of seminiferous tubules, a dramatic decrease in serum levels of testosterone, and a reduction in StAR and 3beta-HSD gene expression. In age-matching VIP KO males, the levels of serum testosterone and steroidogenic enzymes were still very low. Interestingly, in contrast to that observed in young mice, testicular degeneration at 15 months was significantly less severe in VIP KO than WT mice. All together, these results suggest that 1) VIP is an important factor for regulating testosterone biosynthesis and FSH secretion and 2) VIP may influence testicular aging.
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PMID:Lack of vasoactive intestinal peptide reduces testosterone levels and reproductive aging in mouse testis. 1759 29

Oestrogens and glucocorticoids are important for spermatogenesis and are regulated via aromatase for oestradiol synthesis and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD 2) as an inactivator of cortisol. In the present study postnatal changes of these two enzymes were monitored together with testicular development and hormone concentrations. Pigs were assigned to three periods: Weeks 0-5, Weeks 5-11 or Weeks 11-17. In Period 1, groups of four piglets were killed after each week. Blood plasma and testes were sampled immediately post mortem. For Periods 2 and 3, groups of six pigs were fitted with vein catheters for daily blood collection. Testes from all pigs were obtained after killing. Levels of testosterone, oestradiol, LH, FSH and cortisol were determined radioimmunologically. The 11beta-HSD 2- and aromatase-expressing cells were stained immunocytochemically. All hormones were maximal 2 weeks after birth. A rise of LH, testosterone and oestradiol occurred again at Week 17. FSH and cortisol remained basal. Parallel to the first postnatal rise, the presence of aromatase and 11beta-HSD 2 in Leydig cells increased, together with germ and Sertoli cell numbers. Expression was low from 3 to 5 weeks, was resumed after Week 5 and was maximal at Week 17. The amount of 11beta-HSD 2 in germ cells was greatest at birth, decreased thereafter and was absent after Week 3.
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PMID:Aromatase and 11beta-hydroxysteroid dehydrogenase 2 localisation in the testes of pigs from birth to puberty linked to changes of hormone pattern and testicular morphology. 1846 13

Activation of the protein kinase A (PKA) signaling system is necessary for FSH-induced granulosa cell differentiation, but it is not known whether activation of PKA is sufficient to account for the complex pattern of gene expression that occurs during this process. We addressed this question by infecting granulosa cells with a lentiviral vector that directs the expression of a constitutively active mutant of PKA (PKA-CQR) and compared the cellular responses to PKA-CQR with cells stimulated by FSH. Expression of PKA-CQR in undifferentiated granulosa cells resulted in the induction of both estrogen and progesterone production in the absence of cAMP. The stimulatory effects of both PKA-CQR and FSH on estrogen and progesterone production were suppressed by the PKA inhibitor H-89 and were mimicked by PKA-selective cAMP agonists. mRNA levels for P450scc and 3beta-HSD were induced to a similar extent by FSH and PKA-CQR, whereas mRNA levels for P450arom and the LHr were induced to a greater extent by FSH. Microarray analysis of gene expression profiles revealed that the majority of genes appeared to be comparably regulated by FSH and PKA-CQR but that some genes appear to be induced to a greater extent by FSH than by PKA-CQR. These results indicate that the PKA signaling pathway is sufficient to account for the induction of most genes (as identified by microarray analysis), including those of the progesterone biosynthetic pathway during granulosa cell differentiation. However, optimal induction of aromatase, the LHr, and other genes by FSH appears to require activation of additional signaling pathways.
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PMID:Constitutively active protein kinase A qualitatively mimics the effects of follicle-stimulating hormone on granulosa cell differentiation. 1853 49

Carbosulfan an acaricide was orally administrated at 48 mg/kg body weight/day to female swiss albino mice for 5, 10, 20 and 30 d. Daily vaginal smear and body weight was recorded. The mice were sacrificed by cervical dislocation after 24 h of terminal exposure to carbosulfan. The results of the present study indicated that there was a significant decrease in the number of estrous cycle and phases with a concomitant increase in the length of the estrous cycle and diestrus phase with carbosulfan treatment for 10, 20, and 30 d. There was a significant decrease in the weight of the ovary, uterus, number of healthy follicles and increase in the number of atretic follicles with 20 and 30 d carbosulfan treatment when compared with the control. There was a significant decrease in the level of sialic acid with an increase in the level of cholesterol by carbosulfan treatment for 20 and 30 d. The decreased level of sialic acid indicates the decreased level of circulating FSH/LH. The ovary 3beta HSD activity decreased significantly with 20 and 30 d carbosulfan exposure mice indicating its effect on steroidogenesis, when compared to controls. The above findings may be due to direct effect on the ovary or on the gonadotrophins secretion via central nervous mechanism in mice.
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PMID:Effects of carbosulfan administration schedules on estrous cycle and follicular dynamics in albino mice. 1854 80

The potential health hazard of the large amounts of Lead that occurs in canned baby food, domestic water from lead-lined tanks and, in printing and petroleum industries. Lead acetate administration at a does of 8 mg/kg body weight for 21 days resulted a significant increase in adrenal steroidogenic enzyme (Delta5-3beta- HSD) and serum levels of corticosterone, while serum levels of testosterone, FSH, LH and testicular spermatogenesis were decreased in albino rats. But lead-treated rats received exogenous testosterone for the last 14 days of lead treatment, showed prevention of adrenocortical hyperactivity by decreasing adrenal Delta5-3beta-HSD activity and serum level of corticosterone. Testosterone administration also increased serum level of testosterone, FSH and LH along with spermatogenesis. The results suggest that testosterone supplementation in lead-treated rats protects adrenocortical activity and testicular spermatogenesis.
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PMID:Protection of adrenal and male gonadal functions by androgen in lead-treated rats. 1860 1


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