UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of androgen in the sexual dimorphism in hypothalamic growth hormone (GH)-releasing hormone (GHRH) and somatostatin (SS) gene expression was examined in rats. In the first study, the SS and GHRH mRNA levels were measured in both male and female rats at 4, 6, 8, and 10 weeks of age. A significant sex-related difference in the SS and GHRH mRNA levels was observed after 8 weeks of age, when sexual maturation is fully attained. Male rats had higher SS and GHRH mRNA levels than the female rats. In the second study, adult ovariectomized rats received daily injection of dihydrotestosterone (DHT), nonaromatizable testosterone, at a dose of 2 mg/rat for 21 days. The DHT treatment masculinized the GH secretory pattern, which was indistinguishable from that of intact male rats, and simultaneously augmented the SS and GHRH mRNA levels. The DHT treatment of ovariectomized rats after hypophysectomy significantly raised the level of SS mRNA, but not that of GHRH mRNA compared to the control animals. These findings suggest that the activation of the SS gene expression through androgen receptor plays an important role in the maintenance of sexual dimorphism in GH secretion in rats.
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PMID:Masculinization of growth hormone (GH) secretory pattern by dihydrotestosterone is associated with augmentation of hypothalamic somatostatin and GH-releasing hormone mRNA levels in ovariectomized adult rats. 138 27

We have studied the regulation of somatostatin (SS) and growth hormone-releasing hormone (GHRH) gene expression in the brain of the laboratory rat. We report that hypophysectomy in the adult male reduces SS mRNA in cells of the periventricular nucleus (PeN), while GH reverses this effect. We demonstrate that cellular levels of SS mRNA in the PeN are higher in male compared to female animals. We report that castration reduces cellular levels of GHRH mRNA and SS mRNA in the arcuate nucleus and PeN, respectively, and that testosterone reverses this effect through an androgen receptor-dependent mechanism. Finally, we present a theoretical model to explain the generation of the ultradian rhythm in GH secretion, which implicates the reciprocal interaction between GH feedback and the transcriptional regulation of the SS and GHRH genes and the kinetics of these relationships.
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PMID:Regulation of somatostatin and growth hormone-releasing hormone gene expression in the rat brain. 197 20

Growth hormone (GH) secretory patterns are influenced by sex steroids, at least in part, through modulation of the secretion of hypothalamic somatostatin (SS) and GH-releasing hormone. Neurons in the periventricular nucleus (PeN) expressing the messenger RNA (mRNA) for SS are modulated by physiological levels of testosterone. However, it is uncertain whether testosterone's action is mediated directly by androgen receptor activation or indirectly through aromatization to estradiol and subsequent binding to the estrogen receptor. We examined this question by evaluating the effectiveness of 17 beta-estradiol and the nonaromatizable androgen, dihydrotestosterone (DHT), to mimic the effects of testosterone. Adult male rats were castrated and implanted subcutaneously with a Silastic capsule that contained either testosterone, 17 beta-estradiol or DHT, or a sham capsule. Intact animals were sham-operated. We used in situ hybridization to assess the effect of these treatments on SS mRNA signal levels in individual neurons of the hypothalamus. Following castration, SS mRNA content was reduced in cells of the PeN (intact, 195 +/- 12 grains/cell, vs. castrated, 139 +/- 4 grains/cell). Replacement with physiological levels of testosterone prevented the decline in SS mRNA signal levels (castrated testosterone-replaced, 214 +/- 15 grains/cell) as did replacement with the nonaromatizable androgen DHT (castrated DHT-replaced, 213 +/- 16 grains/cell). Treatment with 17 beta-estradiol failed to prevent the postcastration decline in SS mRNA content (castrated estrogen-replaced, 145 +/- 4 grains/cell). Castrated 17 beta-estradiol-treated animals were not significantly different from the castrated sham-treated animals (castrated, 139 +/- 4 grains/cell, vs. castrated estrogen-replaced, 145 +/- 4 grains/cell).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin messenger RNA in hypothalamic neurons is increased by testosterone through activation of androgen receptors and not by aromatization to estradiol. 197 39

To investigate the role of somatostatin (SRIF) in regulating sexually dimorphic GH secretion, we used a reverse hemolytic plaque assay and acutely dispersed somatotropes from age-matched normal male, normal female, and androgen receptor-deficient, testicular feminized (Tfm) rats. Hemolytic plaques were developed after a 90-min incubation in the presence of GH antiserum, 10 nM GH-releasing hormone (GHRH), and the following concentrations of SRIF: 0, 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 nM. Additional studies were performed with 0 or 100 nM SRIF in the absence of GHRH. The absolute number of somatotropes (x10(6); mean +/- SEM) recovered from the pituitaries of Tfm rats (1.73 +/- 0.18) was significantly greater than that from the males (1.11 +/- 0.13; P = 0.01); the number from female rats (1.30 +/- 0.15) was not different from that of either male or Tfm animals. GHRH-stimulated GH secretion, as estimated by the mean GH plaque area (micron2 x 10(4); mean +/- SEM) in the absence of SRIF, was greater for somatotropes from male rats (3.36 +/- 0.41) than that for either Tfm (2.27 +/- 0.32; P = 0.02) or female (1.78 +/- 0.24; P = 0.001) rats; values for the latter two groups did not differ. However, mean GH plaque areas for each group during maximal SRIF inhibition in either the presence or absence of GHRH were indistinguishable from each other and from mean plaque areas obtained under basal conditions. As demonstrated by a lesser EC50 value (0.04 +/- 0.02 nM; mean +/- SEM), somatotropes from female rats were more sensitive to the inhibitory effect of SRIF than were those from either male (EC50 = 1.82 +/- 0.45; P = 0.0001) or Tfm (EC50 = 0.74 +/- 0.22, P = 0.0001) rats; values for the latter two groups were indistinguishable. These observed differences suggest that gender and/or the gonadal hormone environment may be important determinants of the inhibitory effects of SRIF on GH secretion by the somatotrope. While these gender-associated differences may represent effects of the gonadal hormones directly on the somatotrope, they could reflect modulation of the secretion of hypothalamic SRIF and/or GHRH by the prevailing gonadal hormone environment. Such gender-related differences may contribute to the overall sex-dependent patterns of GH secretion in the intact animal.
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PMID:Somatostatin inhibition of growth hormone secretion by somatotropes from male, female, and androgen receptor-deficient rats: evidence for differing sensitivities. 257 9

Gonadal steroids exert important feedback influences on hypothalamic neurones involved in regulating reproductive behaviour and pituitary hormone secretion. The recent development of antibodies specific for individual gonadal steroid receptors has been of great use in determining precisely which cells in the hypothalamus express androgen, oestrogen and progesterone receptors. In the sheep brain, both oestrogen and androgen receptor antibodies have been used successfully and the distribution of cells expressing both receptors has now been determined in ewes and rams, respectively. In addition, the predominantly nuclear localization of the steroid receptors has enabled double-labelling immunocytochemical procedures to determine the neurochemical phenotype of neurones expressing the steroid receptor. Work in the sheep hypothalamus shows that gonadotrophin-releasing hormone neurones do not possess oestrogen or androgen receptors. However, substantial numbers of cells containing oestrogen receptors in the preoptic area of ewes contain the inhibitory neurotransmitter gamma aminobutyric acid, while most oestrogen receptor-immunoreactive neurones in the ventromedial nucleus synthesize the inhibitory neuropeptide somatostatin. Androgen receptors have been detected in many of the ventromedial somatostatin neurones in rams. In contrast, the neurochemical phenotype of the great majority of oestrogen and androgen receptor-immunoreactive cells in the arcuate nucleus remains unknown. The identification of the neurotransmitters and neuropeptides synthesized by neurones possessing androgen and oestrogen receptors in different regions of the ovine hypothalamus provides a neuroanatomical basis for understanding the mechanisms by which gonadal steroids regulate reproductive function.
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PMID:Neurochemical identity of neurones expressing oestrogen and androgen receptors in sheep hypothalamus. 762 19

This study tested for the presence of androgen receptor-immunoreactivity in somatostatin, galanin, vasopressin, corticotropin-releasing hormone, and oxytocin neurons in the rat forebrain. The brains of adult male Sprague-Dawley rats were fixed with 4% paraformaldehyde. Androgen receptor was visualized in coronal sections using nickel intensification of diaminobenzidine, and the neuropeptides were identified using a brown diaminobenzidine reaction product. Androgen receptor was localized to the nuclei of neurons in the septum, amygdala, cortex, hippocampus, and hypothalamus. The majority of somatostatin-containing neurons in the periventricular hypothalamic nucleus also contained androgen receptor. Androgen receptor was also found within galanin-expressing cells in the bed nucleus of the stria terminalis and in the amygdala. Androgen receptor was not observed in corticotropin-releasing hormone, vasopressin, or oxytocin neurons in all areas examined. The data suggest that androgens may be capable of directly regulating somatostatin-expressing neurons of the periventricular nucleus of the hypothalamus and galanin-containing neurons of the bed nucleus of the stria terminalis and amygdala.
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PMID:Localization of androgen receptor within peptidergic neurons of the rat forebrain. 785 Apr 90

Androgen and androgen receptor (AR) play an important role in sexual differentiation and prostate proliferation. To investigate AR gene transcriptional regulation, a 2.3-kilobase AR gene promoter region was isolated, sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and sequence homology search of AR gene promoter among human, rat, and mouse revealed some potential cis-acting elements, including a GC box, a suppressor region, and a purine-rich element. Deletion analysis and gel retardation assay using a 50-base pair (bp) double-strand purine-rich element showed that this purine-rich element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells and may be essential for AR gene transcription. Furthermore, to investigate the effect of cAMP on AR gene transcription, we treated LNCaP and HeLa cells with 10 mM (Bu)2cAMP after transfection with CAT gene reporter plasmids linked to the AR gene promoter. This treatment induced several folds of CAT activity in LNCaP cells only, and the induction was further confirmed at AR mRNA level by Northern blot analysis and reverse transcription-polymerase chain reaction assay. Deletion analysis of the AR gene promoter showed that a region between 530 bp and 380 bp upstream of AR gene transcription initiation site, which includes one potential cAMP response element (CRE), is responsible for cAMP induction. Gel retardation analysis using this CRE (AR/CRE1) showed that AR/CRE1 can bind to specific proteins in nuclear extract of LNCaP cells, which appears to form a different binding complex compared to somatostatin/CRE.
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PMID:Identification of 3',5'-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter. 815 32

The influence of a somatostatin analogue, SMS 201-995 (SMS), on the growth of an androgen-dependent mouse mammary tumor, Shionogi carcinoma 115 (SC115), was studied. Treatment of SC115 tumor-transplanted male mice with s.c. injections of SMS (0.04, 0.2, 1, and 5 micrograms twice a day) resulted in a dose-dependent inhibition of tumor growth. The growth-inhibitory effect of SMS reached its peak at a dose of 1 microgram twice a day. SMS was found not to elicit its growth-inhibitory effect through lowering plasma testosterone levels or down-regulating androgen receptor of SC115 tumors. Since specific binding sites for somatostatin were not observed in the membrane fractions of SC115 tumors and SMS did not inhibit the proliferation of primarily cultured SC115 tumor cells, a direct inhibitory mechanism of SMS on SC115 tumors was unlikely to be operative. Since SMS is a very potent inhibitor of growth hormone (GH) secretion, it was speculated that SMS might inhibit the growth of SC115 tumors indirectly through down-regulation of plasma GH levels. This possibility was evaluated by studying the influence of GH replacement on the growth of SC115 tumors grown in SMS-treated mice. GH replacement was done both in a male secretory pattern (intermittent injection, human GH 500 micrograms/kg twice a day) and in a female secretory pattern (continuous infusion, 1000 micrograms/kg/day). Intermittent injections of GH fully restored the growth of SC115 tumors in the SMS-treated mice to that in the normal controls but continuous infusion of GH was without effect. These results suggest that SMS inhibits the growth of SC115 tumors through suppression of GH secretion, and that the mode of GH administration is an important determinant of its action on SC115 tumor growth.
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PMID:Inhibitory effect of a somatostatin analogue (SMS 201-995) on the growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). 834 Feb 54

Testosterone exerts important feedback effects on the hypothalamus of the ram to influence reproductive functioning. To provide a neuroanatomical basis for understanding this androgen action, the present study has examined androgen receptor (AR) immunoreactivity within the hypothalamus and adjacent brain areas of the intact non-breeding season ram. The largest populations of AR-immunoreactive cells were detected in the medial preoptic area, infundibular and premammillary nuclei in addition to the ventromedial nucleus (VMN) where cells were found distributed throughout its medial and lateral divisions. Smaller numbers of AR-expressing cells were identified in the bed nucleus of the stria terminalis and anterior hypothalamic area (AHA) including the paraventricular, but not the supraoptic, nucleus. Double-labelling immunocytochemistry revealed the presence of AR immunoreactivity in only 2 of 460 gonadotropin-releasing hormone (GnRH) neurons. A very small population of TH-immunoreactive cells located in the lateral aspect of the AHA was found to contain ARs. Dopaminergic cells elsewhere in the hypothalamus, including the infundibular nucleus, did not display AR immunoreactivity. Nearly 50% of AR-expressing cells in the lateral VMN were immunoreactive for somatostatin while less than 5% of periventricular somatostatin neurons displayed AR immunoreactivity. These results show where ARs are expressed in the ram hypothalamus and indicate the neuroanatomical sites at which androgen may act to influence reproductive function. The absence of ARs in the neuroendocrine GnRH and tuberoinfundibular dopaminergic cells suggests that androgens do not influence the genome of these cells in any direct manner. In contrast, the somatostatin neurons of the VMN appear to be an important target for circulating androgens in the non-breeding season ram.
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PMID:Androgen receptor-immunoreactive cells in ram hypothalamus: distribution and co-localization patterns with gonadotropin-releasing hormone, somatostatin and tyrosine hydroxylase. 905 76

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

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