Effect of GHRP-6 and ghrh on gh secretion in rats following chronic glucocorticoid treatment

Voltz, Donald M.; Piering, Andrew W.; Giustina, Matthew Magestro Andrea; Wehrenberg, William B.

doi:10.1016/0024-3205(94)00478-b

Cited by 16 publications

(6 citation statements)

References 29 publications

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“…Although all rats responded with an increase in GH, this was also blunted in those animals with high initial corticosterone levels. This is in good agreement with other data showing that the GH response to GHRP-6 is significantly reduced after chronic dexamethasone treatment in rats (28) and that the GH response to a low dose (0.2 g/kg) of L-692,429 is attenuated after glucocorticoid therapy in man (29). Cushing patients also show a reduced response to GHRP-6 (30), but Giustina et al (31) found that the GH response to hexarelin was not affected in acromegalic patients with glucocorticoid excess.…”

Section: Discussionsupporting

confidence: 93%

Activation of the Hypothalamo-Pituitary-Adrenal Axis by the Growth Hormone (GH) Secretagogue, GH-Releasing Peptide-6, in Rats

Thomas¹,

Fairhall²,

Robinson³

1997

Endocrinology

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GH-releasing hexapeptide (GHRP-6) is a synthetic secretagogue that stimulates the release of GH by acting at both hypothalamic and pituitary sites. GHRPs also consistently elicit small, but significant, increases in plasma concentrations of ACTH and adrenal steroids. As these secretagogues do not release ACTH directly, they probably interact with the hypothalamic peptidergic systems controlling ACTH release, such as CRH and arginine vasopressin (AVP). We have now examined the activation of the hypothalamo-pituitary-adrenal axis by GHRP-6 in conscious rats. In a series of experiments, rats were injected i.v. with 10 microg GHRP-6, 2 microg CRH, 0.5 microg AVP, or saline, alone or in combination, and serial plasma samples withdrawn and assayed for ACTH, corticosterone, and GH. CRH and AVP increased plasma ACTH levels in all rats, whereas ACTH and corticosterone responses to GHRP-6 were variable and were dependent on the prevailing activity of the hypothalamo-pituitary-adrenal axis. GHRP-6 stimulated the largest ACTH responses in rats that had the lowest basal plasma ACTH and corticosterone levels before GHRP-6 administration. GHRP-6 given in combination with CRH did not increase ACTH levels beyond the response to CRH alone (change in ACTH, 1570 +/- 207 vs. 1714 +/- 245 pg/ml), whereas the combination of GHRP-6 and AVP markedly increased ACTH levels compared with the effects of AVP alone (change in ACTH, 5587 +/- 669 vs. 2338 +/- 451 pg/ml; P < 0.05). The GH responses to GHRP-6 were significantly greater in rats with low basal plasma ACTH and corticosterone levels than in rats with elevated ACTH and corticosterone levels (change in GH response, 119 +/- 27 vs. 29 +/- 7 ng/ml; P < 0.01). CRH alone significantly inhibited GH release (pre- vs. 40 min post-CRH, 11.9 +/- 3.8 vs. 1.7 +/- 0.4 ng/ml; P < 0.05), whereas AVP alone had no effect on GH levels. Neither CRH nor AVP had any effect on the GH response to GHRP-6. We suggest that GHRP-6 acts via the hypothalamus to mediate the release of ACTH, and that these effects are probably mediated at least in part via the release of endogenous CRH and are subject to regulation by circulating glucocorticoids.

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Section: Discussionsupporting

confidence: 93%

Activation of the Hypothalamo-Pituitary-Adrenal Axis by the Growth Hormone (GH) Secretagogue, GH-Releasing Peptide-6, in Rats

Thomas¹,

Fairhall²,

Robinson³

1997

Endocrinology

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“…These findings are consistent with several reports on the glucocorticoid-induced inhibition of GH secretion in animal models and in humans (15,18,30). The increases in serum GH concentrations in response to commonly used pharmacological stimuli are typically inhibited in patients with significant endogenous hypercortisolism (10,31).…”

Section: Discussionsupporting

confidence: 92%

Growth Hormone (GH) Responses to GH-Releasing Hormone Alone or Combined with Arginine in Patients with Adrenal Incidentaloma: Evidence for Enhanced Somatostatinergic Tone

Terzolo

Bossoni

Alı̀

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

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Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48 -63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from Ϫ30 to 0 min, and GHRH (100 g) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acidethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 Ϯ 5.2 vs. 18.0 Ϯ 7.0 g/L; P Ͻ 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 Ϯ 20.3 vs. 33.7 Ϯ 17.5 g/L; P ϭ NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 Ϯ 531% vs. 81 Ϯ 45%; P ϭ 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma. (J Cli...

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“…It is well recognized (11) that hypercortisolemia, associated with Cushing syndrome or long-term immunosuppressive therapy, reduces circulating GH levels in humans. Also, prolonged treatment with high doses of dexamethasone decreases basal GH release and hypothalamic GHRH mRNA levels in rats (24,50,58). Taken together, we might speculate that the ability of leptin to reduce circulating glucocorticoids and hypothalamic NPY mRNA levels, relative to pair-fed mice, might contribute to the maintenance of GHRH neuronal activity in the nutrient-deprived state.…”

Section: Discussionmentioning

confidence: 85%

Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice

Luque¹,

Huang²,

Shah³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Leptin-deficient obese mice (ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (approximately 1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.

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Effect of GHRP-6 and ghrh on gh secretion in rats following chronic glucocorticoid treatment

Cited by 16 publications

References 29 publications

Activation of the Hypothalamo-Pituitary-Adrenal Axis by the Growth Hormone (GH) Secretagogue, GH-Releasing Peptide-6, in Rats

Activation of the Hypothalamo-Pituitary-Adrenal Axis by the Growth Hormone (GH) Secretagogue, GH-Releasing Peptide-6, in Rats

Growth Hormone (GH) Responses to GH-Releasing Hormone Alone or Combined with Arginine in Patients with Adrenal Incidentaloma: Evidence for Enhanced Somatostatinergic Tone

Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice

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