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)

9 active acromegalic patients were treated for 12 months with bromocriptine (Parlodel, Sandoz) in a daily dose of 10 mg, and at the end of this treatment a somatostatin infusion was administered. The glucose tolerance and the serum hGH level were determined, and the changes in the clinical symptoms were evaluated. 7 patients (responder group) reacted favourably to the treatment; the other 2 proved to be non-responders, the hGH increasing as a consequence of bromocriptine treatment. The non-responders were among those patients who reacted to hyperglycaemia with a hGH increase (paradox glucose response). The somatostatin infusion employed in the drug treatment caused a very drastic decrease in the hGH level. The biochemical and clinical changes were not synchronous. The results permit the conclusions that (1) a relatively small dose of bromocriptine has a very good effect in the large majority of acromegalic patients; (2) the behaviour of the glucose response is an important point in the differentiation of the non-responders; (3) with somatostatin infusion during bromocriptine treatment a further considerable hGH decrease may be induced (a role is presumably played in the effect by the substitution of the hypothalamically drug-inhibited somatostatin release by exogenous material); (4) there is not a close parallel between the hGH decrease on bromocriptine treatment and the clinical improvement, which indicates the significance of the peripheral effects of the drug.
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PMID:Long-term bromocriptine treatment and somatostatin in acromegaly. 610 52

To determine whether increments in circulating GH concentrations within the physiological range would exert insulin-like as well as insulin-antagonistic actions in man and, if so, whether both actions would occur in hepatic and extrahepatic tissues, normal volunteers (n = 6) were infused with human GH (hGH; 100 ng/kg . min) for 6 h along with somatostatin (100 micrograms/h) to suppress insulin, glucagon, and hGH secretion and also with sufficient insulin (100 microU/kg . min) to maintain a constant plasma insulin level. During the final 2 h, glucose (2 mg/kg . min) was infused. In control studies, saline was infused instead of hGH. Infusion of hGH increased plasma hGH to 35 ng/ml. Plasma glucose decreased to 60 +/- 2 mg/dl compared to 67 +/- 1 mg/dl observed in control studies (P less than 0.05); this greater hypoglycemia was due to both greater suppression of hepatic glucose production (P less than 0.05) and greater augmentation of glucose clearance (P less than 0.05). These insulin-like effects of hGH were no longer evident after 2 h. Subsequently, when glucose was infused, plasma glucose increased to 133 +/- 4 mg/dl compared to the 104 +/- 6 mg/dl observed in control studies (P less than 0.01). This greater hyperglycemia was due to both impaired suppression of hepatic glucose production (P less than 0.001) and decreased glucose clearance (P less than 0.01). These results indicate that physiological increments in plasma hGH cause both insulin-like and insulin-antagonistic effects in man and that these actions occur in hepatic as well as extrahepatic tissues. The insulin-like actions of hGH are transient.
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PMID:Physiological concentrations of growth hormone exert insulin-like and insulin antagonistic effects on both hepatic and extrahepatic tissues in man. 611 64

The metabolic effects of Somatostatin (SRIF) added to insulin were studied in five diabetic subjects with ketonuria induced by insulin withdrawal. In the same patients ketonuria was induced twice and they were randomly treated with insulin alone (10 units as a bolus + infusion 1 U/hr) until euglycemia was reached or with insulin (same criteria) + cyclic SRIF (100 micrograms/ hr i.v.) for ten hours. Treatment with insulin + SRIF significantly reduced both peak and cumulative hGH levels in contrast to insulin alone. Moreover, the percent decrease of glucagon was significantly greater during insulin + SRIF than with insulin alone. On the other hand, the beta-OH levels fell significantly more during insulin + SRIF than during insulin alone. Finally the prolactin plasma levels fell considerably when combined treatment was given but not when just insulin was administered.
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PMID:Effects of somatostatin on established induced ketosis. 612 85

Five female acromegalic patients who had undergone surgical adenomectomy, but still had elevated hGH serum levels, were treated with bromocriptine, 5-15 mg daily, for at least 4 months without a satisfactory response. In an attempt to lower serum hGH levels, p-NH2-Phe4-D-Trp8-somatostatin was administered, 100 micrograms as an i.v. bolus, followed by infusion of 250 micrograms over a 4 hour period. The analogue decreased hGH levels by about 50% in 3 out of 5 patients, both during bromocriptine treatment and also in its absence. Of the remaining two patients, one showed a decrease in hGH levels in response to the analogue only during bromocriptine treatment and the other only without it. Saline infusion after bromocriptine administration did not induce a decrease in hGH levels in three of these patients. Somatostatin analogue caused a fall in serum insulin levels in all but one patient, who had diabetes mellitus and in whom serum insulin was undetectable. Both hGH and insulin levels showed a significant rebound after infusion of the analogue, but returned to basal levels within 24 hours. Prolactin did not change during the analogue infusion in 4 patients with normal PRL levels. However, in one patient in whom prolactin and hGH levels were elevated during bromocriptine treatment, the infusion of somatostatin analogue decreased both hormones. The analogue induced no changes in serum TSH, FSH and LH levels of any of the patients.
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PMID:Effect of a somatostatin analogue on trophic hormone levels in acromegalic patients with elevated hGH after adenomectomy and treatment with bromocriptine. 654 82

Specific lesions in the periventricular area of the hypothalamus in male rats lead to a partial feminization of the liver steroid metabolism and a simultaneous reduction of the somatostatin level in the median eminence. Administration of an antiserum against somatostatin causes a similar degree of feminization of liver metabolism in male rats. Thus somatostatin could be the neuroendocrine regulator of the sexually differentiated metabolism of steroids in rat liver. A possible influence from the amygdaloid complex in regulating hepatic steroid metabolism is also indicated since large lesions in the amygdala cause a slight feminization of hepatic steroid metabolism in male rats. The female pattern of hepatic steroid metabolism is induced following frequent administration of hGH. The feminizing effect of hGH on hepatic steroid metabolism does not require the presence of gonads, adrenals, or thyroid. The somatogenic property of hGH seems to be responsible for the feminizing effect since purified rGH alone gives a complete feminization of hepatic steroid metabolism in hypophysectomized animals. rGH purified from male or female pituitary glands is equally efficient in feminizing hepatic steroid metabolism. Furthermore, male or female rGH have the same apparent molecular weight and isoelectric point. The mechanism whereby GH regulates hepatic steroid metabolism could be related to the sexually differentiated secretory profile of GH in the rat. A continuous presence of GH in the circulation seems to be a prerequisite for a female pattern of hepatic steroid metabolism. By analogy, it may be suggested that the high-peak, low-trough secretory pattern of GH characteristic of male rats causes a masculine type of liver steroid metabolism. Gonadal hormones affect both the secretory profile of GH and hepatic steroid metabolism. It is most probable that gonadal hormones affect liver steroid metabolism via modulations of the GH secretory profile. Possibly, estrogen exerts its effect directly on the pituitary by stimulating GH secretion. Androgen most probably has its primary site of action in the anterior hypothalamus or in extrahypothalamic areas. A plausible mechanism is that androgens stimulate the hypothalamic GH-inhibitory center. An overall view of the present hypothesis concerning hypothalamopituitary regulation of the sexually differentiated hepatic steroid metabolism in the rat is presented in Figure 2.
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PMID:Growth hormone: a regulator of the sexually differentiated steroid metabolism in rat liver. 666 12

In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.
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PMID:Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat. 761 36

Transgenic mice expressing a tyrosine hydroxylase-human (h) GH fusion gene in the hypothalamus exhibit a dwarf phenotype. The GH feedback mechanism(s) underlying the growth retardation in these animals was investigated by assessing peptide and messenger RNA (mRNA) levels of the hormones of the hypothalamic-GH-IGF-I axis. Pituitary GH content, hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) content, and serum IGF-I levels were measured by RIA. mRNA levels of hypothalamic GHRH and SRIH and of pituitary GH and the GHRH receptor were measured by Northern blot hybridization. Transgenic mice of both sexes and their wild-type littermates were studied at 2-4 months of age. The pituitary GH content was markedly reduced by 85% in male and by 87% in female transgenic mice compared to that in wild-type controls (P < 0.01 for both). The pituitary GH mRNA content was also decreased by 73% (P = 0.002) in transgenic male mice. Circulating IGF-I levels were significantly reduced by 66% and 68% in male and female transgenic mice, respectively (P = 0.001). The hypothalamic GHRH content was significantly reduced by 19% and 33% (P < 0.05) in male and female transgenic mice, respectively. No significant difference was detected, however, in the hypothalamic SRIH content between wild-type and transgenic mice. Hypothalamic GHRH mRNA levels were significantly decreased by 35% (P = 0.002) in transgenic male mice compared to those in wild-type littermates. In contrast, SRIH mRNA was not significantly changed. An even greater reduction (61%; P = 0.003) was observed in pituitary GHRH receptor mRNA in transgenic mice. These data indicate that the GH deficiency and dwarf phenotype of the tyrosine hydroxylase-hGH transgenic mouse can be attributed primarily to impaired hypothalamic GHRH production. The mechanism of GH feedback inhibition appears to involve direct suppression of GHRH gene expression by locally produced hGH in the hypothalamus.
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PMID:Autofeedback suppression of growth hormone (GH) secretion in transgenic mice expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking sequences to the hypothalamus. 764 13

In a previous work, we reported that passive immunization with anti-growth hormone-releasing hormone (GHRH) antibodies (GHRH-Ab) in neonatal rats caused disruption of somatotropic function that was still present 60 d posttreatment. We studied the reversibility of this condition by growth hormone (GH) replacement therapy. Neonatal rats received GHRH-Ab (50 microL/rat, s.c.) or normal rabbit serum every second day from birth up to postnatal d 10 and received hGH (0.4 microgram/g body weight, s.c., b.i.d.) or vehicle in a 2 x 2 factorial design. Animals were studied on d 11 of age. In GHRH-Ab-treated rats, GH therapy 1) counteracted the reduced body weight and low plasma IGF-I levels; 2) failed to modify the reduced pituitary weight and GH content; 3) further reduced the low plasma GH levels; 4) partially restored the defective GH responsiveness to GHRH; 5) failed to modify the reduced hypothalamic somatostatin and increased GHRH gene expression in the hypothalamus; and 6) reverted the decreased pituitary somatostatin binding. Morphologic and morphometric evaluation of the pituitary gland from GHRH-AB+GH pups showed that the number of GH-labeled structures was lower than in normal rat serum-GH-treated pups, whereas the total GH immunoreactivity per unit surface, an index of intracellular hormone concentration, was slightly higher than in vehicle-GH or GHRH-Ab pups. As determined by electron microscopy, somatotropes from GHRH-Ab+GH pups had morphologic features of high cellular activity. It appears that in GHRH-deprived pups GH replacement therapy can normalize most but not all altered indices of the somatotropic function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatotropic dysfunction in growth hormone-releasing hormone-deprived neonatal rats: effect of growth hormone replacement therapy. 780 27

Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH-producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH-immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two-fold increase (P < 0.01) relative to control animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH) was comparable for transgenic and control mice. Total SRIH mRNA in situ hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of all transgenic mice compared with controls, and was not elevated in the MBH. The higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight gain, but not to greater SRIH expression than in other GH-transgenic mice, suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH-transgenic mice may represent a plateau of maximal feedback stimulation. The results indicate that lifelong elevated heterologous GH in mice stimulates hypothalamic SRIH expression markedly. It is not known whether this mechanism is direct or indirect via a mediator of GH such as IGF, but the heterologous GH appears to be specific to these hypophysiotropic neurons.
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PMID:Increased hypothalamic somatostatin expression in mice transgenic for bovine or human GH. 782 24

In 8- and 20-month-old male rats, treated or not with growth hormone (GH) for 4 days, simultaneous evaluation of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SS) gene expression, GH secretion from anterior pituitaries (APs) in vitro (basal and GHRH-stimulated) and plasma IGF-I levels was performed. Twenty-month-old rats showed decreased GHRH mRNA levels, decreased GH secretion from APs in vitro (not responsive to GHRH stimulation) and reduced plasma IGF-I levels as compared to younger counterparts. SS mRNA levels were only slightly reduced in the hypothalamus of aged rats. Short-term administration of biosynthetic human GH (125 microgram/rat, twice daily, IP) to 8-month-old rats abolished the in vitro GHRH-stimulated GH release from APs and altered GH regulatory neuropeptides gene expression, i.e., reducing GHRH mRNA levels and increasing SS mRNA levels. In 20-month-old rats, hGH administration increased plasma IGF-I levels but did not change significantly GHRH and SS gene expression. These data indicate that the feedback effects exerted by circulating GH on GHRH and SS neurons, while evident in adult rats, are not detectable in aged rats.
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PMID:Feedback effects of growth hormone on growth hormone-releasing hormone and somatostatin are not evident in aged rats. 790 38


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