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

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotransmitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypothalamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.
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PMID:Transmitter content and afferent connections of estrogen-sensitive progestin receptor-containing neurons in the primate hypothalamus. 135 61

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene (DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 microgram, 0.2 microgram, 1 microgram, 5 micrograms, and 20 micrograms. Buserelin was used in a 2 x 5 micrograms/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progesterone (PgR) receptor contents of the mammary tumors were not changed. In contrast, buserelin treatment caused highly significant tumor remission. The combined treatment with sandostatin and buserelin did not alter the treatment results obtained after treatment with buserelin alone. In conclusion, sandostatin treatment in this tumor model had no direct growth inhibitory effect and did not cause an endocrine inhibition of mammary tumor growth. However, these results do not exclude antitumor effects in human breast cancer in view of the presence of somatostatin receptors in approximately 20-45% of human tumors, besides possible different endocrine effects.
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PMID:The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors. 196 5

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

Female rats were treated in vivo with estrogen for three weeks. The pituitaries were then removed and their responses to somatostatin, dopamine, TRH, hGHRH(1-44)NH2, or their combination were examined in a superfused pituitary cell system. Somatostatin did not decrease basal prolactin secretion in the control cells, but it caused a dose-dependent decrease in prolactin release from the estrogen pretreated cells. Estrogen pretreatment did not alter the sensitivity of pituitary cells to dopamine; dopamine was equally effective in the control and estrogen pretreated pituitaries in decreasing the basal prolactin secretion and TRH induced prolactin release. Prolactin release from the estrogen pretreated cells, stimulated by 25 nM TRH was inhibited by 1 nM somatostatin and nearly totally abolished by 25 nM somatostatin, whereas in the control cells only the higher dose of somatostatin caused some decrease in the prolactin release. Estrogen pretreated cells showed a reduced response to GHRH. Somatostatin did not decrease the basal secretion of GH in either group, but at 1 nM dose it completely abolished the GH release induced by equimolar concentration of GHRH. However, after somatostatin was eliminated from the system, a delayed GH release could be observed that was greater in the control pituitaries than in the estrogen pretreated pituitaries. It is concluded that in vivo treatment with estrogen reduces GH secretion in response to GHRH and increases prolactin secretion after TRH stimulation. After estrogen treatment, the basal and TRH stimulated prolactin release can be effectively reduced by somatostatin. These effects could be observed in vitro using estrogen free tissue culture medium for up to 36 hours after the removal of the pituitaries. The reciprocal changes in GH and prolactin secretion support the concept of the transdifferentiation of GH and prolactin secreting cells.
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PMID:Reciprocal changes in prolactin and growth hormone secretion in vitro after in vivo estrogen treatment. 772 21

In the guinea pig, steroid target cells reside in the ventrolateral hypothalamic nucleus (VLH), an important site in the mediation of female receptive behavior, and in the arcuate nucleus (AR), a structure essential for stimulation effects of ovarian hormones on gonadotropin secretion. However, the mechanisms by which these steroid-dependent reproductive neuroendocrine processes occur are only partially understood. Estrogen is known to affect the hypothalamus content of certain neuropeptides. In the present study, we investigated the effects of estradiol benzoate (EB) on immunoreactivity of neurons containing one of three following neuropeptides: somatostatin (SOM), neurotensin (NT) and substance P (SP) in VLH and AR. The number of immunoreactive (IR)-neurons was quantified in anatomically matched sections through VLH and AR of ovariectomized (OVX), OVX + EB and OVX + oil-treated guinea pigs. Analysis of variance revealed that the number of SOM-IR and SP-IR neurons significantly increased in all regions of VLH of OVX + EB-treated guinea pigs as compared to OVX or OVX + oil-treated animals (P < 0.01) but showed no EB effect on the number of NT-IR neurons. Although the number of SOM-IR and NT-IR neurons slightly increased following treatment with EB in AR, analysis of variance revealed no significant change. The present results provide additional information relevant to possible involvement of these neuropeptides in facilitation of female typical sexual behavior.
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PMID:Estrogen modulation of neuropeptides: somatostatin, neurotensin and substance P, in the ventrolateral and arcuate nuclei of the female guinea pig. 1021 66

The sst2 somatostatin receptor mediates the inhibitory effects of somatostatin on secretive and proliferative processes. We previously showed that sst2 is one of the major subtypes expressed in the rat pituitary, and its messenger RNA level is up-regulated by chronic treatment with estrogen. To investigate the molecular mechanisms regulating sst2 gene expression, we cloned the upstream region (9.5 kb) from the translation initiation codon of the rat sst2 gene. It contained a single intron (5.0 kb) at the 5'-untranslated region, lacked TATA and CCAAT boxes, and had multiple transcriptional start sites. Transient transfection analysis with deleted mutants of a luciferase reporter construct showed that the promoter activity was regulated negatively and positively in the distal and proximal promoter regions, respectively. The promoter activity of each construct was more efficient in GH(3) pituitary cells than in nonpituitary cells. The construct (-77/+172/luc) containing a cAMP response element (CRE; -54/-47) provided maximum promoter activity, but a further 5'-deleted construct dramatically reduced the activity. Competitive gel shift and supershift assays indicated that Sp2 and Sp3 were bound to an Sp1 site (-40/-31), and activating transcription factor-2 and c-Jun were bound to a CRE site. Both Sp1 and CRE sites were essential for the full promoter activity. Overexpression of the pituitary homeoprotein Pitx1 activated the promoter activity of the -4066/+172/luc construct, and mapping analysis indicated the existence of two Pitx1 response sites, including the CRE site. Estrogen also increased the promoter activity of -77/+172/luc in GH(3) cells or in HeLa cells overexpressing both the estrogen receptor and c-Jun. These studies demonstrated the nature of the rat sst2 gene and the functional importance of both Sp1 and CRE sites in regulating sst2 gene expression and suggest that the CRE site mediates, at least partly, the promoter activity activated by Pitx1 or estrogen.
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PMID:Characterization of 5'-flanking region of rat somatostatin receptor sst2 gene: transcriptional regulatory elements and activation by Pitx1 and estrogen. 1125 Sep 22

Estrogen is the proximate sex steroid sustaining GH secretion throughout the human life span in both sexes. However, very little is known about the specific neuroendocrine mechanisms by which estrogen activates and maintains GH secretion in the young or aging human. The identification of somatostatin in 1973 as a key negative peptidyl regulator of the GH axis and the discovery of GH-releasing hormone (GHRH) in 1982 as a dominant feedforward agonist of GH secretion provided an initial basic science foundation for exploring sex-steroid control of the GH-IGF-1 axis. Although GH-releasing peptides (GHRPs) were first recognized in 1977-1981, subsequent cloning of hypothalamopituitary receptors transducing potent secretagogue actions of GHRPs in 1996 and of an endogenous ligand for this effector pathway in 1999 now extend the framework for examining the mechanisms of estrogen-driven GH secretion in aging. Herein, we review several novel and multifaceted interactions in postmenopausal women between estrogen and GHRP-2. We combine these observations into a simplified construct of GH-axis neuroregulation comprising the somatostatin, GHRH, and GHRP effector pathways, as well as GH and IGF-1 autofeedback. We suggest the thesis that estrogen controls the interfaces among these pivotal regulatory peptides in hyposomatotropic postmenopausal individuals.
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PMID:Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2. 1132 1

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.
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PMID:Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion. 1144 79

As an indirect probe of estrogen-regulated hypothalamic somatostatin restraint, the present study monitors the ability of short-term oral E2 supplementation to modulate GH secretion during combined continuous stimulation by recombinant human GHRH [GHRH-(1-44)-amide] and the potent and selective synthetic GH-releasing peptide, GHRP-2. According to a simplified tripeptidyl model of GH neuroregulation, the effects of estrogen in this dual secretagogue paradigm should mirror alterations in endogenous somatostatinergic signaling. To this end, seven healthy postmenopausal women underwent frequent (10-min) blood sampling for 24 h during simultaneous i.v. infusion of GHRH and GHRP-2 each at a rate of 1 microg/kg x h on d 10 of randomly ordered placebo or 17beta-estradiol (E2) (1 mg orally twice daily) replacement. Serum GH concentrations (n = 280/subject) were assayed by chemiluminescence. The resultant GH time series was evaluated by deconvolution analysis, the approximate entropy statistic, and cosine regression to quantitate pulsatile, entropic (feedback-sensitive), and 24-h rhythmic GH release, respectively. Statistical comparisons revealed that E2 repletion increased the mean (+/- SEM) serum E2 concentration to 222 +/- 26 pg/ml from 16 +/- 1.7 pg/ml during placebo (P < 0.001) and suppressed the serum LH by 48% (P = 0.0033), serum FSH by 64% (P < 0.001), and serum IGF-I by 44% (P = 0.021). Double peptidyl secretagogue stimulation elevated mean 24-h serum GH concentrations to 8.1 +/- 1.0 microg/liter (placebo) and 7.7 +/- 0.89 microg/liter (E2; P = NS) and evoked prominently pulsatile patterns of GH secretion. No primary measure of pulsatile or basal GH release was altered by the disparate sex steroid milieu, i.e. GH secretory burst amplitudes of 0.62 +/- 0.93 (placebo) and 0.72 +/- 0.16 (E2) microg/liter x min, GH pulse frequencies of 27 +/- 1.8 (placebo) and 23 +/- 1.9 (E2) events/24 h, GH half-lives of 12 +/- 0.74 (placebo) and 15 +/- 4.5 (E2) min, and basal (nonpulsatile) GH secretion 70 +/- 22 (placebo) and 57 +/- 18 (E2) ng/liter x min. The approximate entropy (ApEn) of serial GH release [1.297 +/- 0.061 (placebo) and 1.323 +/- 0.06 (E2)] and the mesor (cosine mean), amplitude, and acrophase (time of the maximum) of 24-h rhythmic GH secretion were likewise invariant of estrogen supplementation. Estimated statistical power exceeded 90% for detecting significant (P < 0.05) within-subject changes exceeding 30-50% in the mean serum GH concentration, GH ApEn, or GH mesor. In contrast, ApEn analysis of the evolution of successive GH secretory burst-mass values over 24 h disclosed that E2 replacement disrupts the serial regularity of pulsatile GH output (elevates the ApEn ratio) during combined GHRH/GHRP-2 stimulation (P = 0.004). In summary, short-term elevation of serum E2 concentrations in postmenopausal individuals into the midfollicular phase range observed in young women does not significantly alter 24-h basal, pulsatile, entropic, or nyctohemeral GH secretion monitored under continuous combined drive by GHRH and GHRP-2. As E2 repletion without enforced GHRH/GHRP-2 stimulation augments each of the foregoing regulated facets of GH release, we infer that one or both of the infused peptidyl secretagogues may itself participate in E2's short-term amplification of GH secretion in postmenopausal individuals. Estrogen's disruption of the orderliness of sequential GH pulse-mass values during fixed GHRH/GHRP-2 feedforward would be consistent with a subtle reduction in the release and/or actions of hypothalamic somatostatin or an (unexpected) direct pituitary action of the sex steroid. Whether comparable dynamics mediate the effects of endogenous estrogen on the GH axis in premenopausal women or pubertal girls is not known.
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PMID:Impact of estradiol supplementation on dual peptidyl drive of GH secretion in postmenopausal women. 1183 33

A number of hormones, including hypothalamic neuropeptides acting as neurotransmitters and neuromodulators in the CNS, are involved in the physiologic regulation of breathing and participate in adjustment of breathing in disease. In addition to central effects, some hormones also control breathing at peripheral chemoreceptors or have local effects on the lungs and airways. Estrogen and progesterone seem to protect from sleep-disordered breathing, whereas testosterone may predispose to it. Progesterone and thyroxine have long been known to stimulate respiration. More recently, several hormones such as corticotropin-releasing hormone and leptin have been suggested to act as respiratory stimulants. Somatostatin, dopamine, and neuropeptide Y have a depressing effect on breathing. Animal models and experimental human studies suggest that also many other hormones may be involved in respiratory control.
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PMID:Hormones and breathing. 1247 61


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