Somatostatin Receptors in Human Growth Hormone and Prolactin- Secreting Pituitary Adenomas

Moyse, Emmanuel; Dafniet, M. Le; Epelbaum, Jacques; Pagésy, Patrick; Peillon, F; Kordon, C.; Enjalbert, A

doi:10.1210/jcem-61-1-98

Cited by 84 publications

(24 citation statements)

References 26 publications

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“…1). They were characterized by different groups [10][11][12], As the other authors, we found that the density of SRIH receptors was highly vari able among the different adenomas tested. However, in our study, we found an inverse correlation between the number of SRIH receptors and the plasma GH levels ( fig.…”

Section: Trh Receptorssupporting

confidence: 75%

“…It has not been demon strated that SRIH or SRIH analogues were able to reduce in vivo PRL secretion [13]. However, recently, an in vitro inhibition of PRL secretion from human adenoma tous and normal lactotropes has been demonstrated [ 14], We found high-affinity SRIH-binding sites on the mem branes of PRL-secreting adenomas with characteristics similar to those obtained on GH-secreting adenoma membranes [11]. However, the number of binding sites was 4 times lower than that found in GH-secreting ade nomas (Bmax = 37 ± 9 fmol/mg protein) and there was no correlation between the density of SRIH-binding sites and the plasma PRL levels.…”

Section: Trh Receptorssupporting

confidence: 73%

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Receptors and Neurohormones in Human Pituitary Adenomas

Peillon

Dafniet²,

Garnier³

et al. 1989

Horm Res

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In order to go further into the pathogenesis of human pituitary adenomas, we studied receptors for neurohormones (thyroliberin, TRH; dopamine, DA; somatostatin, SRIH), for estradiol and epidermal growth factor (EGF) thought to influence hormone secretion and/or cell growth. The following results were obtained: (1) the receptors listed above, with the exception of EGF receptors in the adenomas, are present in normal pituitary tissue and in prolactin (PRL)- and growth hormone (GH)-secreting adenomas; (2) they are functional and their affinities are not different in normal or tumoral tissues; (3) their density is variable and depends on the type of secreting adenoma (GH or PRL), the size of the tumor and the plasma level of the hormone which is secreted, and (4) in nonsecreting adenomas, only TRH receptors are found with characteristics identical to those observed in secreting adenomas. We also showed that TRH is contained in normal and tumoral pituitary tissues. TRH and SRIH are released in vitro from adenomatous cells in large amounts, suggesting their possible synthesis by the pituitary. In both cases a local regulation is observed. TRH release is stimulated in the presence of DA while SRIH is inhibited in the presence of TRH. This neuropeptide release may be implicated in the pituitary hormone regulation through a paracrine or an autocrine mechanism. Thus, the neurohormone receptors found in pituitary adenomas should be dependent on a more complex regulation than it has been envisaged till now.

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Section: Trh Receptorssupporting

confidence: 75%

Section: Trh Receptorssupporting

confidence: 73%

Receptors and Neurohormones in Human Pituitary Adenomas

Peillon

Dafniet²,

Garnier³

et al. 1989

Horm Res

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“…In analogy, a similar mechanism of somatostatin may exist in the pituitary. For the investigation of the mechanism of somatostatin action in the pituitary, human GH-producing pituitary tumor cells are useful because the presence of somatostatin receptors in the cell membrane has been demonstrated (12)(13)(14) and the inhibition of GH secretion by somatostatin has been reported (15)(16)(17)(18)(19). In the present study we investigated the response of the membrane potential to somatostatin in dissociated human pituitary adenomas that secreted GH, and we found that somatostatin increased the K+ conductance.…”

Section: Introductionmentioning

confidence: 68%

Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone.

Yamashita¹,

Shibuya²,

Ogata³

1986

Proc. Natl. Acad. Sci. U.S.A.

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Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 ± 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage damp condition an outward K+ current, a tetrodotoxinsensitive Na+ current, and a Ca2' current were observed. Cobalt ions suppressed the-Ca2+ current. The threshold of Ca2' current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 ± 4.3 mV in 6 mM K+ medium and -97.2 ± 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to KV.The hyperpolarized membrane potential induced by somatostatin was -63.6 ± 5.9 mV in the standard medium. This level was subthreshold for Ca2' and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions.Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca21 currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.Somatostatin (somatotropin release-inhibiting factor, SRIF) is a potent inhibitor of growth hormone (GH) secretion. It also inhibits the secretion of other pituitary hormones (1, 2) and extrapituitary hormones (3). GH secretion is known to be regulated by the level of intracellular cyclic AMP (cAMP), which is raised by a stimulatory hormone, such as GHreleasing factor (4). It has been claimed that somatostatin exerts its inhibitory action through the reduction of cAMP production (5-7).Ca2l is another important factor that controls GH secretion from the anterior pituitary. It has been shown that Ca2l is required for GH release evoked by high concentrations of extracellular K+ (8) and GH-releasing factor (4, 9). Various anterior pituitary cell lines have b*,n shown to have action potentials that are dependent on Ca2l or Na+ (10). The influx of Ca2l is postulated to be controlled at least partly by the action potential. The membrane-signal transduction mechanism for somatostatin action has not yet been fully clarified in the pituitary. In the rat pancreas islet it has been reported that somatostatin activates a K+ conductance and inhibits glucose-induced insulin release (11). In analogy, a similar mechanism of somatostatin may exist in the pituitary. For the investigation of the mechanism of somatostatin action in the pituitary, human GH-producing pituitary tumor cells are useful because the presence of somatostatin receptors in the cell membrane has been demonstrated (12...

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“…3], In vitro studies of GH-secreting pituitary adenomas demon-stratcd a direct inhibitory effect of SRIH on GH secretion [4,5]. This effect is mediated through specific SRIH receptors characterized on rat somatotrophs [6] as well as on GH-secreting adenomas [7][8][9], The action of SRIH on pituitary somatotrophs is mediated through multiple mechanisms involving the inhibition of adenylate cyclase [10][11][12], the opening of K+ channels [13] and the subse quent closing of voltage-dependent Ca2+ channels [ 14], Originally, the variability of in vivo, as well as in vitro, GH response to SRIH in GH-secreting pituitary tumors [2,5,15] was attributed to the very short half-life of the native peptide. The development of potent long-acting SRIH analogs was of major importance in the treatment of acromegaly [for review, see 16].…”

Section: Introductionmentioning

confidence: 99%

Resistance to Somatostatin (SRIH) Analog Therapy in Acromegaly

Bertherat

Chanson²,

Dewailly³

et al. 1992

Horm Res

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The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated ( > 10 µg/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the α subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (Gas). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites. Taken together, these findings suggest that in addition to a lack of SRIH-binding sites on some rare octreotide-resistant GH-secreting tumors, other mechanisms could be involved in the differential sensitivity to SRIH analogs.

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Somatostatin Receptors in Human Growth Hormone and Prolactin- Secreting Pituitary Adenomas

Cited by 84 publications

References 26 publications

Receptors and Neurohormones in Human Pituitary Adenomas

Receptors and Neurohormones in Human Pituitary Adenomas

Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone.

Resistance to Somatostatin (SRIH) Analog Therapy in Acromegaly

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