Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of various hormones and growth factors on aromatase activity in cultured human skin fibroblasts. Several potential trophic factors were tested for their ability to modify basal aromatase activity or the response to dibutyryladenosine 3',5'-cyclic monophosphate and dexamethasone because (i) no endogenous ligand has been identified that is responsible for stimulating aromatase activity in the periphery, and (ii) dexamethasone and cAMP analogs can increase this enzyme's activity in fibroblasts. The effect of insulin and insulin-like growth factors were examined in closer detail because of the clinical association between insulin and hyperandrogenism. Pituitary hormones and hypothalamic releasing factors, such as human ACTH (10 nM), beta-endorphin (10 nM), beta-lipotropin (10 nM), alpha-MSH (10 nM), gamma 3-MSH (10 nM), ovine luteinizing hormone (10 ng/ml), ovine follicle-stimulating hormone (10 ng/ml), ovine thyroid-stimulating hormone (10 ng/ml), rat growth hormone (10 ng/ml), rat prolactin (10 ng/ml), rat corticotropin-releasing factor (10 nM), luteinizing hormone-releasing factor (10 nM), thyrotropin-releasing factor (10 nM), human growth hormone-releasing factor (10 nM), and somatostatin (10 nM), have no significant effects on aromatase activity. Porcine inhibin A (10 ng/ml) and porcine activin AB (10 ng/ml), two ovarian hormones with structural transforming homology to transforming growth factor-beta, also have no effect on aromatase activity. Although basic fibroblast growth factor (1-100 ng/ml), acidic fibroblast growth factor (1 ng/ml), epidermal growth factor (1 ng/ml), platelet-derived growth factor (1 ng/ml), tumor necrosis factor (1 ng/ml), and transforming growth factor-beta 1 (1 ng/ml) have no effect on basal aromatase activity in human skin fibroblasts, all of these growth factors inhibited the ability of dibutyryladenosine 3',5'-cyclic monophosphate to stimulate aromatase activity. In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM). Thus, there is a clear distinction between the effects of dexamethasone and cAMP on peripheral aromatase. On the basis of the results presented here, it is interesting to speculate that the hyperandrogenism that is often associated with insulin resistance may be due to a combination of growth factor-mediated inhibition of aromatase activity and the failure of peripheral tissues to respond to insulin and metabolize androgens to estrogens.
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PMID:Growth factor-mediated regulation of aromatase activity in human skin fibroblasts. 167 98

Prostatic cancer is often locally advanced or metastatic when diagnosed, making surgical removal and radiotherapy ineffective treatments. Alternative therapy involves androgen deprivation because prostatic cancer is known to be androgen-dependent. Orchidectomy has proved effective but other methods of reducing androgen concentrations have also been developed. Oestrogens have proved effective, as have progestogens, and both steriodal and non-steroidal anti-androgens have been extensively studied. Another possible treatment is the use of inhibitors of androgen metabolism (aromatase and 5 alpha-reductase). Luteinizing hormone releasing hormone analogues, which act as antagonists or agonists, have been shown to have efficacies comparable to those of other therapies. Adrenal suppression has provided a useful alternative to adrenalectomy, particularly because of the high morbidity rate of surgery in elderly patients. Complete androgen withdrawal using an anti-androgen in association with surgical or chemical castration may be a more superior treatment. Another possible approach is the use of somatostatin analogues, which have been shown to inhibit the growth of animal prostatic cancer cells.
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PMID:Prostatic cancer--survey of hormonal treatment in Europe. 218 53

Although aromatase activity is exceptionally high in the teleost pituitary, it is not known which of the secretory cell types are responsible. Pituitary glands from the longhorn sculpin (Myoxocephalus octodecimspinosus) were sectioned transversely into "cephalic" and "caudal" fragments and cultured for 24 hr in medium containing [7-3H]androstenedione. Radiolabeled estrone and estradiol-17 beta production were measured as an estimate of aromatization. In order to determine the distribution pattern of different cell types, the in situ pituitary and dissected fragments were analyzed by standard cytological procedures. Further verification of cell function was obtained by somatostatin (SRIF) and corticotropin-releasing factor (CRF) immunocytochemistry. Estrogen yields obtained from caudal fragments in two separate experiments averaged four times higher per milligram protein than yields from matched cephalic fragments. In addition, female glands synthesized significantly more estrogen than those of males. Due to an anteroflexion of the longitudinal axis and a disposition of the gonadotropic (GTH) cells at the periphery of the gland and surrounding the neurointermediate lobe (NIL), the classical subdivisions of the teleost adenohypophysis were not strictly applicable to the sculpin. The predominance of growth hormone (GH) secreting cells in the caudal fragment suggests their participation in aromatization, a finding which is consistent with a previous study of rodent pituitary; however, a role for gonadotropes and other hypophysial cells in this transformation cannot be ruled out.
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PMID:Distribution of cell types and aromatase activity in the sculpin (Myoxocephalus) pituitary. 286 48

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to prevent other follicles from developing at the same time as dominant follicle. These other follicles remain quiescent or evaluate to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of estrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching metaphase of the second meiotic division. Several factors are involved in the inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin and oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.
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PMID:Endocrine, paracrine and autocrine control of follicular development. 329 54

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to avoid other follicles developing at the same time as the dominant follicle. These other follicles remain quiescent or go on to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of oestrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching the metaphase of the second meiotic division. Several factors are involved in this inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin, oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.
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PMID:[Endocrine, paracrine and autocrine mechanisms involved in follicular development]. 333 Jul 30

To date, very few studies on the effect of somatostatin on female reproductive function have been reported. In our study, we examined the effects of somatostatin on (i) androgen biosynthesis using whole ovarian dispersates, and (ii) aromatase activity and progesterone production using granulosa cells. Whole ovarian dispersates obtained from immature rats were cultured for 96 h in serum-free medium with human chorionic gonadotrophin (HCG; 25 ng/ml) and insulin (10 micrograms/ml) in the presence or absence of an increasing concentration of somatostatin (0.03-3.00 ng/ml). HCG- and insulin-stimulated accumulation of androsterone by these cells was inhibited significantly by somatostatin. Granulosa cells from diethylstilbestrol-treated rats were cultured for 48 h in serum-free medium with follicle-stimulating hormone (FSH; 20 ng/ml) and FSH plus insulin (1 microgram/ml) with or without somatostatin (0.03-3.00 ng/ml). Both aromatase activity and progesterone production stimulated by FSH and FSH plus insulin were significantly inhibited by somatostatin. Somatostatin by itself (1 ng/ml) did not have an effect on any of the evaluated parameters. The action of somatostatin could be immunoneutralized and did not influence the plated viable cell mass. These findings indicate that somatostatin can regulate ovarian steroidogenesis by mediating gonadotrophin and growth factor action on different ovarian cell types.
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PMID:Somatostatin action on rat ovarian steroidogenesis. 856 24

Adult hamsters were exposed to short-photoperiod, and injected with either somatotropin (GH), somatostatin (GHRIH), or saline for eight weeks. Hamster testis fragments of similar size were incubated with or without hCG. No significant differences in the basal media testosterone and estradiol levels were observed among groups. Treatment with GH potentiated the hCG-dependent increase in media testosterone. Contrary to what was expected, treatment with GHRIH did not only not reduce the hCG-related elevation in media testosterone, but even produced a numerical increase of it. Treatment with GHRIH potentiated the hCG-dependent increase in media estradiol, whereas treatment with GH produced only a numerical increase of the response. Furthermore, the combined exposure to GHRIH and hCG appeared to cause an increase in the efficiency of testicular aromatase. Since previous data indicated that the combined deficiency of lactotropic and somatotropic actions severely impairs testicular steroidogenesis, treatment with GHRIH should have caused further steroidogenic impairment in hamsters exposed to short-photoperiod. Since this does not appear to be the case, it could be postulated that GHRIH has a direct stimulatory or at least a protective effect on testicular steroidogenesis.
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PMID:Effects of somatostatin and somatotropin on the in vitro testicular steroidogenesis in hamster. 890 32

Endocrine therapy of breast cancer consists of a variety of both medical and surgical ablative treatment modalities, but ablative therapy is increasingly replaced by medical treatment. Most endocrine therapies have more than one endocrine effect, frequently together with direct growth inhibitory actions via receptors. Endocrine therapy can be effective in all phases of the disease, but curative only in early disease while in advanced cancer it can only prolong survival. In the past decade the number of available endocrine agents has been drastically increased. Novel approaches in the endocrine therapy of breast cancer are application of new antiestrogens, antiprogestins, new potent aromatase inhibitors, analogues of luteinizing hormone-releasing hormone (LHRH-A) and somatostatin, inhibitors of prolactin secretion, vitamin A and D analogues, bisphosphonates, growth factor antagonists, tyrosine protein kinase inhibitors, protease inhibitors, inhibitors of angiogenesis, radiolabeled hormones and monoclonal antibodies. New cell biological factors such as oncogenes and suppressorgenes, secretory proteins and membrane receptors can be used not only as prognostic factors but also for prediction of type of response to endocrine and chemotherapy. Thus, these cell biological parameters can be used to select high and low risk patients, type of systemic treatment, and can also be used as targets for new treatment modalities. Future studies on treatment of all stages of disease will increasingly focus on promising combined treatment modalities.
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PMID:Novel endocrine therapies in breast cancer. 914 62

The sexually dimorphic profile of GH secretion is thought to be engendered by gonadal steroids acting in part on hypothalamic periventricular somatostatin (SOM) neurons. The present study set out to examine and characterize the development of sex differences in these SOM neurons. In the first series of experiments, we used in situ hybridization to examine SOM messenger RNA (mRNA) expression within the periventricular nucleus (PeN) of male and female rats on postnatal day 1 (P1), P5, and P10. Cellular SOM mRNA content was found to increase from P1 to P10 in both sexes (P < 0.01), but was 24% (P < 0.05) and 38% (P < 0.01) higher in males on P5 and P10, respectively. A second series of experiments examined the SOM peptide content of the PeN in developing rats and found increasing levels from P1 to P10, with a 44% higher SOM content in males compared with females on P10 (P < 0.05). The third series of experiments questioned the role of gonadal steroids in engendering sex differences in SOM mRNA expression by determining the effects of neonatal gonadectomy (GDX) and replacement of dihydrotestosterone or estradiol benzoate. The SOM mRNA content of PeN neurons in P5 males gonadectomized on the day of birth was the same as that in P5 females and was significantly reduced compared with that in sham-operated P5 males (P < 0.05). Male rats GDX on P1 and treated with estradiol benzoate from P1 to P5 had cellular SOM mRNA levels similar to those in intact males on P5, whereas dihydrotestosterone treatment had no effect. Treatment of intact males with an androgen receptor antagonist, cyproterone acetate, on P1 had no effect on cellular SOM mRNA on P5, whereas male rats given the aromatase inhibitor 1,4,6-androstatriene-3,17-dione from P1 to P5 had lower (P < 0.05) SOM mRNA levels than controls. In the final set of experiments, dual labeling immunocytochemistry showed that SOM neurons in the PeN of P5 rats did not contain estrogen receptor-alpha, but expressed androgen receptors in a sexually dimorphic manner. These results demonstrate that a sex difference in SOM biosynthesis, which persists into adulthood, develops between P1 and P5 in PeN neurons. Despite the absence of estrogen receptor-alpha in these neurons, the organizational influence of testosterone only occurs after its aromatization to estrogen.
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PMID:Estrogen-dependent ontogeny of sex differences in somatostatin neurons of the hypothalamic periventricular nucleus. 949 79

Recently, our laboratory has identified three distinct pre-pro-somatostatin (PSS) genes in goldfish brain: PSS-I encodes for somatostatin (SRIH)-14, PSS-II encodes SRIH-28, which contains [Glu(1), Tyr(7), Gly(10)] SRIH-14 at its C-terminus, and PSS-III encodes [Pro(2)] SRIH-14. In goldfish, increasing levels of the sex steroid estradiol increase the plasma levels of growth hormone (GH). However, whether sex steroids act at the level of the brain to regulate GH release is unclear. In the present study, the effects of sex steroids on the expression of the three PSS genes in goldfish forebrain were examined. The results demonstrate that treatment with estradiol significantly increases the expression of PSS-I and PSS-III genes in both male and female fish. The effects of estradiol were evident after only 2.5 days of treatment. Testosterone treatment increased the expression of PSS-I and PSS-III genes in female but not male fish, and only at the highest dose used. In addition, the effects of testosterone were evident only after treatment for 5 or 10 days and were blocked by an aromatase inhibitor, suggesting that testosterone must be converted to estradiol to exhibit the effect. Neither estradiol nor testosterone treatment had effects on the expression of the PSS-II gene. These results suggest that sex steroids can act either directly or indirectly on the brain to regulate PSS-I and PSS-III gene expression, influencing in turn the regulation of GH secretion.
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PMID:Regulation of expression of somatostatin genes by sex steroid hormones in goldfish forebrain. 1209 12


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