Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone

Bélanger, Alain; Labrie, Fernand; Borgeat, Pierre; Savary, Muriel; Côté, James E.; Drouin, Jacques; Schally, Andrew V.; Coy, David H.; Coy, Esther J.; Immer, H.; Sestanj, K.; Nelson, V.; Götz, Manfred

doi:10.1016/0303-7207(74)90022-7

Cited by 59 publications

(13 citation statements)

References 18 publications

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“…There are conflicting reports regarding the effects of SRIF on 1552 DORFLINGER AND SCHONBRUNN Endo • 1983 Volll3«No5 cAMP levels in the anterior pituitary (3,12,(15)(16)(17)(18)(19)(20). Furthermore, SRIF inhibits stimulation of GH secretion by cAMP analogs (21)(22)(23)(24) and phosphodiesterase inhibitors (16,(19)(20)(21)24). The latter results indicate that SRIF can inhibit pituitary hormone release by a mechanism that is independent of an effect on cAMP concentration.…”

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confidence: 76%

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

1983

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Somatostatin (SRIF) inhibits both basal and vasoactive intestinal peptide (VIP)-stimulated hormone secretion by the GH4C1 clonal strain of rat pituitary tumor cells. We have previously shown that SRIF inhibits cAMP accumulation stimulated by VIP but does not alter basal cAMP levels in this cell line. To determine the importance of changes in cAMP accumulation in the mechanism of SRIF action, we have compared the effect of SRIF on hormone release stimulated by VIP and two other secretagogues which increase effective intracellular cAMP concentrations: forskolin and 8-Bromo-cAMP (8-Br-cAMP). VIP stimulated GH and PRL secretion to the same maximal extent (220% of control) with similar ED50 values (0.37 +/- 0.03 and 0.43 +/- 0.08 nM, mean +/- SE, respectively). SRIF (100 nM) reduced maximal VIP-stimulation of both GH and PRL release from 220 to 140% of control; however, it did not significantly change the ED50 values for VIP. The effect of SRIF on VIP-stimulated hormone release parallels its action on VIP-stimulated cAMP accumulation. Furthermore, the concentrations of SRIF required to produce half-maximal inhibition of VIP-stimulated GH and PRL release (0.8 +/- 0.2 nM and 0.7 +/- 0.1 nM, respectively) were similar to its potency to inhibit VIP-stimulated cAMP accumulation (1.2 +/- 0.1 nM). These data indicate that changes in cAMP levels mediate inhibition of VIP-stimulated hormone secretion by SRIF. Forskolin increased cAMP accumulation with an ED50 value of 2.4 +/- 0.5 microM. A maximal concentration of forskolin (100 microM) stimulated cAMP accumulation to a greater extent than 100 nM VIP (34 +/- 4-fold vs. 9 +/- 1-fold). Together, forskolin (100 microM) and VIP (100 nM) stimulated cAMP accumulation by more than 50-fold. However, PRL secretion in response to maximal concentrations of VIP or forskolin individually or together were the same (approximately 200% of control). These results support the conclusion that both compounds stimulate PRL secretion by a cAMP-mediated mechanism which can be fully activated by either one alone.(ABSTRACT TRUNCATED AT 400 WORDS)

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confidence: 76%

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

1983

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“…It is well established that SS can exert a potent inhibitory action on thyrotropin [4][5][6] as well as on PRL secretion (in the presence of E2) both in vitro and in vivo in the rat [1,5,7,8]. Moreover, several studies indicate that PRL may modulate TIDA neuronal activity [25-27 and refs therein].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to suppressing GH secretion, SS exerts a direct inhibitory action on thyrotropin se cretion by the anterior pituitary gland [4][5][6]. Moreover, SS has been found to decrease prolactin (PRL) secretion [5], the in hibitory effect being estrogen-dependent, at least in the rat [1,7,8], Somatostatin has been detected in the secretory granules of a few neurons located in the periventricular nucleus (PeN) of the rat hypothalamus [2,9].…”

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confidence: 99%

Multihormonal Control of Pre-Pro-Somatostatin mRNA Levels in the Periventricular Nucleus of the Male and Female Rat Hypothalamus

et al. 1990

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The influence of sex steroids as well as the possible involvement of dopaminergic pathways in the modulation of pre-pro-somatostatin (SS) mRNA levels was investigated by quantitative in situ hybridization in the hypothalamic periventricular nucleus (PeN) in adult male and female rats. In situ hybridization was performed using a [³⁵S]-labeled cDNA probe encoding pre-proSS mRNA. Gonadectomy performed 14 days earlier decreased the mean number of silver grains/neuron corresponding to the relative pre-proSS mRNA levels by 22% in male and by 18–28% in female rats. A 14-day treatment with the nonaromatizable androgen dihydrotestosterone (DHT) increased the mean number of silver grains/neuron by 34–40%) in gonadectomized animals of both sexes. Moreover, administration of 17β-estradiol (E₂, 0.25 µg twice daily) increased pre-proSS mRNA levels by 40% in ovariectomized (OVX) animals. Such treatment with E₂ or DHT changed the frequency distribution profile of the hybridization signal intensity, thus increasing the percentage of highly labeled neurons (>61 grains/neuron) by 10 to 12-fold. A 14-day treatment with the D₂ dopamine receptor agonist bromocriptine (BRO) increased pre-proSS mRNA levels by 15 and 28% in intact female and OVX animals, respectively, while the dopaminergic antagonist haloperidol (HAL) decreased the value of this parameter by 20 and 30%. Furthermore, BRO increased pre-proSS mRNA levels by 10 and 20% in intact and castrated male rats, respectively, whereas HAL decreased pre-proSS mRNA levels by 25 and 14% in the same groups of animals. Administration of E₂ in combination with HAL in OVX animals increased pre-proSS mRNA levels by 70% compared to those measured in OVX animals treated with HAL alone. In HAL-treated castrated male rats, administration of DHT increased the relative pre-proSS mRNA levels by 35% compared to those measured in castrated animals treated with HAL alone. The present data clearly demonstrate that androgens and estrogens as well as dopamine-mediated mechanisms could play a regulatory role in pre-proSS mRNA levels in somatostatinergic neurons in the hypothalamic PeN in both male and female rats.

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“…Somatostatin is found in classic 'open type' endocrine cells from which it is directly excreted into the blood [4], paracrine cells with long cytoplasmic extensions which terminate on putative effector cells [5] and in neurones where it may function as a neurotransmitter [6][7][8] or is released from the nerve endings into the blood [4]. Thus, depending on its site of elaboration, somatostatin may function as a hormone, a neurohormone, a neurotransmitter or a parahormone.…”

Section: Introductionmentioning

confidence: 99%

Somatostatin Analogs in Oncology: A Look to the Future

Jenkins

Kynaston²,

Davies³

et al. 2001

Chemotherapy

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In the past 15 years considerable advances have been made in our understanding of the molecular pharmacology of the mechanisms whereby somatostatin and its analogs mediate their direct and indirect antineoplastic effects. However, some important issues remain to be resolved, in particular the functional roles of the individual somatostatin receptors (SSTR-1–5) in tumor tissue and up- or downregulation of the hSSTRs with prolonged administration of somatostatin analogs. Answers to these questions are essential before we can maximize the therapeutic efficacy of somatostatin analogs in cancer. For example, is continuous administration more or less effective than intermittent therapy? The role of somatostatin analogs in the management of acromegaly and to a lesser extent neuroendocrine tumors is firmly established. The development of depot preparations of all 3 somatostatin analogs currently available for clinical use will undoubtedly improve both patient compliance and quality of life in patients with these conditions. There are only likely to be minor differences in the therapeutic efficacy of octreotide, lanreotide and vapreotide since all three analogs exert the majority of their antineoplastic effects via hSSTR-2 and hSSTR-5 and at the end of the day, price may well dictate which of these drugs oncologists use to provide symptomatic palliation of acromegaly and neuroendocrine tumors. Apart from some notable exceptions, somatostatin analog therapy has proven to be very disappointing in the management of advanced malignancy. Improvements in the management of solid tumors are likely to come only from combination therapy of somatostatin analogs with cytotoxic agents or other hormones in both advanced malignancy and in the adjuvant setting. Clinical trials with clear-cut objective outcome measures and health-related quality of life assessment are needed to evaluate the therapeutic efficacy of combination treatment in advanced malignancy and as an adjuvant to surgery. Particular attention needs to be paid to possible adverse effects of somatostatin analog therapy on the immune response to cancer. Further studies are required to establish whether the adverse effects of somatostatin analog therapy alone or in combination with cytotoxics or other hormones can be reversed with appropriate immunomodulatory treatment. Targeted somatostatin analog radiotherapy and chemotherapy are currently being investigated and the results of these studies are awaited with interest. Novel approaches using combinations of somatostatin analogs with antiangiogenic drugs or gene therapy are of particular interest and may provide important advances in the management of cancer in the not too distant future.

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Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone

Cited by 59 publications

References 18 publications

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

Multihormonal Control of Pre-Pro-Somatostatin mRNA Levels in the Periventricular Nucleus of the Male and Female Rat Hypothalamus

Somatostatin Analogs in Oncology: A Look to the Future

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Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone

Cited by 59 publications

References 18 publications

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells*

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells*

Multihormonal Control of Pre-Pro-Somatostatin mRNA Levels in the Periventricular Nucleus of the Male and Female Rat Hypothalamus

Somatostatin Analogs in Oncology: A Look to the Future

Contact Info

Product

Resources

About

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*