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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of androgens on granulosa cell stimulation by isoproterenol and follicle-stimulating hormone (FSH) were determined. Two functional parameters of granulosa cell stimulation were monitored: (a) activity of a transfected proopiomelanocortin (POMC) promoter and (b) production of progesterone. Treatment with the beta-adrenergic agonist, isoproterenol, stimulated steroidogenesis, and both isoproterenol and FSH appeared to enhance POMC promoter activity. The non-aromatizable androgen, 5 alpha-dihydrotestosterone (DHT), produced no effect on either parameter, but it potentiated the steroidogenic response to isoproterenol. Preliminary data also indicated a potentiation by DHT of the FSH-mediated increase in POMC promoter activity; results with a combination of DHT and isoproterenol were suggestive of potentiation. A possible role for androgen amplification of adrenergic stimulation in polycystic ovarian syndrome is discussed.
Steroids 1989 Dec
PMID:Androgens amplify beta-adrenergic and FSH stimulation of granulosa cells. 251 69

Ovarian steroids and growth factors are intragonadal modulators which augment a key endpoint of follicle-stimulating hormone (FSH) action in granulosa cells: the induction of aromatase activity. Studies of these paracrine hormones that enhance FSH-stimulated estrogen biosynthesis by cultured rat granulosa cells, have led to the development of a sensitive and specific in vitro bioassay for FSH. This newly developed granulosa cell aromatase bioassay (GAB) allows for the measurement of bioactive FSH levels in serum and urine of humans and animals with various physiological and pathological conditions. These studies have demonstrated that the GAB assay is useful in detecting possible changes in the molecular forms of FSH. The adaptation of this method for urine samples allows for the measurement of bio-FSH levels in situations where venipuncture is not practical or in species for which specific radioimmunoassays are not available.
Steroids
PMID:Use of the granulosa cell aromatase bioassay for measurement of bioactive follicle-stimulating hormone in urine and serum samples of diverse species. 314 63

To determine the molecular basis for changes in aromatase (P450arom) activity in rat ovarian follicles and corpora lutea, seven clones for rat P450arom cDNA have been identified and isolated from a rat granulosa cell lambda gt11 cDNA expression library using a 62 mer deoxyoligonucleotide probe (derived from an amino acid sequence of purified human placental aromatase) and a human placental P450arom cDNA probe. One of the rat P450arom cDNA clones contained an insert 1.2 kb in size. Both the human 1.8 kb cDNA and the rat 1.2 kb cDNA probes hybridized to a single species of P450arom mRNA that was 2.6 kb in size. Northern blot analysis revealed that corpora lutea isolated on day 15 of pregnancy contained high amounts of P450arom mRNA, whereas granulosa cells of antral follicles of hormonally primed, hypophysectomized rats (i.e., those from which mRNA was isolated to construct the cDNA library) contained only low amounts of P450arom mRNA. The lower amounts of P450arom in granulosa cells of preovulatory follicles in the estradiol-follicle-stimulating hormone primed hypophysectomized rats were unexpected because follicles incubated in medium containing testosterone substrate produce more estradiol than do corpora lutea isolated on day 15 of pregnancy and incubated under similar conditions. Additional studies will determine the hormonal events responsible for the elevated amounts and constitutive maintenance of P450arom mRNA and aromatase activity in luteal cells in vivo and in vitro.
Steroids
PMID:Hormonal regulation of estradiol biosynthesis, aromatase activity, and aromatase mRNA in rat ovarian follicles and corpora lutea. 314 64

This study describes the effects of insulin, insulin-like growth factor 1 (IGF1), and epidermal growth factor (EGF) on the aromatase activity of granulosa cells isolated from immature rat ovaries. None of the growth factors alone influenced the basal level of aromatase activity, but did modulate follicle-stimulating hormone (FSH)-induced aromatase activity. Insulin and IGF1 augmented the action of a sub-optimal concentration of FSH (5 ng/mL) on aromatase activity in a dose-dependent manner. In contrast, EGF (1-10 ng/mL) was effective in inhibiting aromatase activity maximally stimulated by FSH. Since insulin and IGF1 had opposing actions to those of EGF on FSH-induced aromatase activity, we examined the interactions between the growth factors. EGF inhibited the actions of both FSH and insulin on aromatase activity. Both IGF1 and EGF increased the [3H]thymidine incorporation into the DNA of bovine granulosa cells in vitro, IGF1 being a more potent mitogen. Whereas EGF inhibited the actions of IGF1 on aromatase activity, it did not inhibit the effects of IGF1 on the growth of granulosa cells. In summary, growth factors influence both the differentiation and growth of granulosa cells, and may be important regulators of follicular development.
Steroids
PMID:Aromatase activity in granulosa cells: regulation by growth factors. 314 65

The hypothesis that cumulus cells inhibit oocyte maturation by a cAMP-dependent process was tested (R.M. Schultz, R. Montgomery, P.F. Ward-Bailey, and J.J. Eppig (1983). Dev. Biol. 95, 294-304.). Treatment of isolated cumulus cell-oocyte complexes with follicle-stimulating hormone (FSH) resulted in a dose-dependent increase in both cumulus cell cAMP levels and in the extent of inhibition of germinal vesicle breakdown (GVBD), the first morphological manifestation of oocyte maturation. Furthermore, it was found that concentrations of a membrane-permeable analog of cAMP, dibutyryl cAMP (dbcAMP), that were below those required for complete meiotic inhibition had a greater inhibitory effect on cumulus cell-enclosed oocytes than on denuded oocytes. Cumulus cell-enclosed and denuded oocytes matured at the same time in the absence of dbcAMP. Ablation of the gap junctions that couple cumulus cells to the oocyte abolished the maturation-inhibitory action of cumulus cells that was promoted either by FSH or low concentrations of dbcAMP. These results are consistent with the hypothesis that inhibition of oocyte maturation is mediated by a factor of granulosa/cumulus cell origin, other than cAMP, which requires cAMP for its activity and/or generation, and an intact intercellular coupling pathway between cumulus cells and the oocyte. A variety of steroid hormones potentiated the FSH-induced inhibition of maturation in cumulus cell-enclosed oocytes. In addition, steroid hormones inhibited maturation in denuded oocytes, but only when oocyte cAMP levels were elevated by cAMP analogs or forskolin. Steroids alone did not inhibit maturation of either cumulus cell-enclosed or denuded oocytes. Moreover, the steroids alone or in combination with FSH did not affect metabolic coupling between the cumulus cells and oocytes, nor did testosterone affect the forskolin-induced level of cAMP in denuded oocytes. Therefore, it is proposed that the oocyte is a site for the synergistic activity of steroid hormones with a cAMP-dependent process in inhibiting maturation. Results of these studies are discussed in terms of the roles of intercellular communication, cAMP, a putative maturation-inhibiting factor, and steroid hormones in the inhibition of maturation of mouse oocytes.
 ...
PMID:Inhibition of oocyte maturation in the mouse: participation of cAMP, steroid hormones, and a putative maturation-inhibitory factor. 619 27

Aromatase (CYP19) mRNA is induced by follicle-stimulating hormone (FSH) in granulosa cells of preovulatory follicles and subsequently is rapidly diminished as a consequence of the luteinizing hormone (LH) surge. Primary cultures of rat granulosa cells were used to identify some of the cellular mechanisms by which FSH increases and LH decreases steady-state levels of aromatase mRNA. Induction of aromatase mRNA by FSH was increased by cycloheximide but was blocked by alpha-amanitin and the C-kinase activators gonadotropin-releasing hormone (GnRH) and phorbol 12-myristate 13-acetate (PMA). In contrast, the decrease in steady-state levels of aromatase mRNA by LH was mimicked by A-kinase (forskolin) and C-kinase (PMA or GnRH) activators. The decrease in aromatase mRNA was associated with decreased amounts of mRNA and protein for steroidogenic factor-1 (SF-1), a nuclear orphan receptor that binds and trans-activates the aromatase promoter, and with the A-kinase subunit type II (RII beta), which is required for mediating cAMP action in these cells. The down-regulation of aromatase, SF-1, and RII beta by each kinase activator and alpha-amanitin was prevented by cycloheximide when the drug was added in combination with the activator. If, however, cycloheximide was added 2 h after PMA (or LH), the drug did not prevent the rapid loss of mRNA. When granulosa cells were transfected with an aromatase CAT transgene, CAT activity was stimulated 10- to 20-fold by FSH and forskolin but not by PMA. Taken together, these results indicate that the A-kinase but not the C-kinase pathway can trans-activate the aromatase gene in immature granulosa cells, whereas the C-kinase, as well as A-kinase pathways, mimic the LH surge to decrease aromatase mRNA in preovulatory cells. By increasing degradation of aromatase mRNA and by inhibiting transcription, the LH surge rapidly terminates the granulosa cell pattern of gene expression while reprogramming the cells to express genes associated with ovulation and luteinization.
Steroids 1997 Jan
PMID:Expression of aromatase in the ovary: down-regulation of mRNA by the ovulatory luteinizing hormone surge. 902 37

In the present study, we investigated the effects of a steroid 5 alpha-reductase inhibitor, finasteride, when given orally (5 mg/day), on the serum levels of gonadal, hypophyseal, and adrenal hormones and the clinical significance of these effects. Forty-eight patients with a mean age of 63 (range 49-81) were included in the study. All patients had symptoms of benign prostatic hyperplasia. Serum levels of testosterone, dihydrotestosterone, follicle-stimulating hormone (FSH) luteinizing hormone (LH), prolactin, aldosterone, cortisol, and dehydroepiandrosterone were determined before the study. The degree of symptoms in each patient and serum prostate specific antigen levels were determined together with uroflowmetric studies. Sexual status of the patients was also assessed with a self-administered questionnaire. All patients received finasteride, 5 mg/day, for 6 weeks. All of the above mentioned studies were repeated at month 3 and month 6. All of the patients had baseline hormonal values within the normal range. At month 3, the dihydrotestosterone level decreased by 60%, while the testosterone level increased by 15%. FSH and LH levels decreased by 24% and 16%, respectively. The changes in the serum levels of these hormones were further evident at month 6. No significant changes were noted in the serum levels of prolactin, aldosterone, cortisol, and dehydroepiandrosterone. Thirty-six patients (75%) were judged to be potent before the treatment. Finasteride caused erectile dysfunction in 8 patients (22%) by month 3 and in 12 (33%) by month 6. A substantial improvement was noted in symptoms of benign prostatic hyperplasia in all patients. The serum prostate specific antigen level decreased by 42% and 50% at month 3 and at month 6, respectively. Continued administration of finasteride, 5 mg/day alters the serum levels of testosterone, dihydrotestosterone, FSH, and LH significantly. Finasteride also causes sexual dysfunction in a substantial number of patients and should be offered with caution to patients who have an active sexual life.
Steroids 1998 Apr
PMID:Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study. 958 55

There is considerable evidence that although estradiol may trigger the preovulatory surge of gonadotropins, progesterone is required for its full magnitude and duration and that glucocorticoids bring about selective follicle-stimulating hormone release. The luteinizing hormone-releasing hormone (LHRH) neuron does not have steroid receptors and is regulated by excitatory amino acid neurotransmission. Steroids do not appear to modulate excitatory amino acid receptors directly but increase release of glutamate in the preoptic area. This may be due to the suppression by steroids of the enzyme glutamatic acid decarboxylase67 that converts glutamate into GABA. NMDA receptors colocalize with nitric oxide synthase-containing neurons that surround the LHRH neurons in the preoptic area and intersect the LHRH fibers in the median eminence. Other potential novel pathways of LHRH release that are currently being explored include carbon monoxide generated by the action of heme oxygenase-2 on heme molecules and bradykinin acting via bradykinin B2 receptors.
Steroids
PMID:Neuroendocrine mechanisms underlying the control of gonadotropin secretion by steroids. 961 80

The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) bind specific receptors, members of the G protein-coupled receptor superfamily. Mutations of gonadotropin receptors are classified into activating (constitutively active or gain-of-function mutations) and inactivating (loss-of-function mutations). Activating mutations of the LH receptor have been described in familial and sporadic forms of male-limited pseudoprecocious puberty, whereas they do not appear to have any particular phenotype in females. The only activating mutation of the FSH receptor described to date was found in a hypophysectomized man who was fertile despite undetectable serum gonadotropin levels; the effects of constitutive FSH receptor activity in the context of normal pituitary function are not known. Homozygous inactivating mutations of the LH and FSH receptor invariably lead to amenorrhea in genotypical female subjects. In males, inactivation of the LH receptor in its more severe form results in a clinical picture similar to the syndrome of complete androgen resistance, but milder forms of hypoandrogenization have been described as well. In males, homozygous inactivation of the FSH receptor can also be associated with infertility. Finally, polymorphic variants of the FSH receptor are present in the normal population.
Steroids
PMID:Molecular pathophysiology and clinical manifestations of gonadotropin receptor defects. 961 88

Hirsutism in adolescent girls commonly starts as an esthetic problem in young women and is later complicated by the development of infertility and polycystic ovary syndrome, which are frequent consequences of prolonged hyperandrogenism. To ascertain whether particular prepubertal clinical manifestations may predict the development of adolescent hirsutism, we followed 70 girls with precocious pubarche (PP) with or without prepubertal hypertrichosis (PH) until 3 years (mean age 14.8 +/- 0.9 years) after menarche. Similar follow-up was carried out in six girls with PP secondary to 21 hydroxylase deficiency (NC-CAH), treated with hydrocortisone. In addition, a retrospective study on the incidence of precocious pubarche was performed in 139 hirsute teenagers (mean age 17 +/- 1.8 years). Testosterone, androstenedione, dehydroepiandrosterone sulphate, 17 alpha-hydroxyprogesterone (basal and after ACTH), luteinizing hormone and follicle-stimulating hormone were evaluated by radioimmunoassay or immunoradio metric assay in the early follicular phase, in cycling subjects. Pelvic ultrasonography was also performed. In the 139 hirsute teenagers, 29 had a history of PP (21% vs. 0.6% in the general Italian population). Of these 139 patients, NC-CAH was diagnosed in 8 (6%), 5 of whom (63%) had PP. Of the 70 girls with PP, hirsutism was present in 44 (63%). PH was present in 37 of 44 patients (84%) with hirsutism, but only in 9 of 26 (35%) without hirsutism. Our results showed that 1) PP represents a risk factor for the development of postpubertal hirsutism; 2) the association with PH seems to increase the risk probability; and 3) patients with hirsutism due to NC-CAH have a higher incidence of PP compared with other hirsute patients, but glucocorticoid treatment in such patients prevents the development of hirsutism. Whether early treatment in the other PP patients may prevent the development of hirsutism remains to be established.
Steroids
PMID:Hyperandrogenism in the adolescent female. 961 92


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