Nonspecific Pituitary Responses to Hypothalamic Hormones in Basic and Clinical Research

Locatelli, Vittorio; Müller, Eugenio E.

doi:10.1007/978-1-4684-4529-9_10

Cited by 11 publications

(5 citation statements)

References 166 publications

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“…The increased GHRH-induced G H response of cirrhotic patients is suggestive of the enhanced G H response to GHRH present in rats passively immunized with a somatostatin antiserum (Wehrenberg et a[., 1982). The presence of a reduced somatostatinergic tone in some cirrhotic patients would be compatible with the high baseline G H levels, and has previously been suggested to explain the paradoxical G H response to TRH and glucose (Miiller et at., 1979;Cocchi et al, 1984). However, the hyperresponsiveness to GHRH in all of our patients, regardless if they had normal or high baseline G H levels or a positive response to TRH, is evidence against an involvement of somatostatin.…”

Section: Discussionmentioning

confidence: 60%

Growth Hormone Hyperresponsiveness to Growth Hormone‐releasing Hormone in Patients With Severe Liver Cirrhosis

Salerno

Locatelli

Müller

1987

Clinical Endocrinology

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Patients with severe liver disease often have high baseline plasma GH levels and/or paradoxical GH release in response to several secretagogues, e.g. TRH. In this paper, we have investigated in a group of cirrhotic patients the GH response to GH-releasing hormone (GHRH) and evaluated the effectiveness of GHRH to cause GH release in TRH responder and non-responder patients. Ten patients and seven age- and sex-matched control subjects were given bolus injections of GHRH (0.1 and 1.0 microgram/kg i.v. on separate occasions). GHRH 0.1 microgram/kg failed to cause a GH response in both control and cirrhotic subjects, but 1.0 microgram/kg caused a significantly higher GH response in patients than in controls. Evaluation of the GH response curve after GHRH revealed a similar pattern of secretion in the TRH-responders (four subjects) and non-responders (six subjects). These results suggest that the enhanced GH responsiveness to GHRH in cirrhotic patients may contribute to their high baseline GH levels and/or secretory rate, and the mechanism(s) of the paradoxical GH rise after TRH seems to be separate from that for GH hyperresponsiveness to GHRH.

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Section: Discussionmentioning

confidence: 60%

Growth Hormone Hyperresponsiveness to Growth Hormone‐releasing Hormone in Patients With Severe Liver Cirrhosis

Salerno

Locatelli

Müller

1987

Clinical Endocrinology

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“…Several other hypothalamic peptides participate in the regulation of Gh, some of them having dual functions depending on age, pathological state, site of action, etc. For instance, thyrotropin releasing hormone (TRH) is stimulatory in fetal and neonatal stages before the somatotropic axis is established or in pathologies such as acromegaly (Cocchi et al, 1983;Harvey, 1990), whereas it inhibits GH release by its action on the hypothalamus (Cocchi et al, 1983;Müller, 1987). CRH, corticotrophin releasing hormone, and neuropeptide Y (NPY) both have an inhibitory effect (Katakami, 1985, Ono et al, 1984McDonald, 1985;Rettori et al, 1990), and both are most likely mediated by SST (Katakami, 1985).…”

Section: Neuroendocrine Regulation Of Gh Synthesis and Secretionmentioning

confidence: 99%

Differential abilities of the chicken Pit‐1 isoforms to regulate the chicken growth hormone promoter

Mukherjee

2011

FASEB j.

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Pit1, a pituitary-specific transcription factor, regulates differentiation of cells of the PIT1 lineage in the anterior pituitary. PIT1 also regulates the synthesis of peptide hormones from these cell types, including growth hormone (GH). A founding member of the POU-homeodomain family of transcription factors, PIT1 is characterized by a serinethreonine rich N-terminal transactivation domain and a C-terminal POU-domain.Alternative forms of PIT1, differing from each other in the N-terminal domain have been reported in several species, but the functional implication of having multiple isoforms is not known. Several Pit1 isoform mRNAs exist in chickens which have not been characterized. The main aim of this study was to determine which, if any, of the chicken PIT1 isoforms regulated the chicken Gh (cGh) promoter. PIT1β2, a novel isoform of chicken PIT1 was discovered, and known and novel isoforms (PIT1α, PIT1β1, PIT1β2 and PIT1γ) were characterized. A luciferase reporter construct containing 1775bp of the cGh promoter driving expression of firefly luciferase was used to determine the ability of the isoforms to regulate the target gene promoter activity in chicken LMH cells. We showed that three of the isoforms, PIT1α, PIT1β1 and PIT1β2, expressed from recombinant plasmids, regulated the cGh promoter, while PIT1γ did not. All the isoforms localized to the nucleus in both non-pituitary and pituitary cells. Results from gel-shift assays show that PIT1γ did not bind the proximal PIT1-binding site of the cGh promoter as well as the other isoforms, suggesting a possible mechanism behind the inactivity. Our result did not suggest a negative regulatory role for this isoform. In contrast, we found a functional advantage for having multiple isoforms. PIT1β1, the isoform that activated the promoter most strongly, when co-transfected with other activating isoforms, such as PIT1α and PIT1β2, induced significantly higher level of activation than one isoform alone. Whether this increased activation required, or was facilitated by, heterodimerization of two isoforms is not known. Nevertheless, identification of isoforms © Copyright by Malini Mukherjee 2011 work that much harder to never fail. Dear daidamoni, my brother, what would I do without you?! Not only do we share our parents, we share our each and every happiness and loss, sadness and elation, together. Sarmila, thank you for joining our family and making our house a home again. Sonali, why didn't I get to know you better years ago? If I had, I am certain I would have not made many of the mistakes I did in my graduate career. Anyway, now that you are here, you are not going anywhere. Thank you! Susmita, I would never have reached this milestone without your help! How can I thank you enough? Thank you for being you; keep smiling, always! I would also like to thank a few dear friends and cousins, many of whom have already been or are currently pursuing the same degree in me. Thank you Tannistha, Sangeeta, Pragati, Dan, Oli, Veena, Piu. Thank you all for all your support. And l...

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“…TRH blocks in humans the GH response to different GH secretagogues [36][37][38]. Moreover, both compounds induce a paradoxical GH rise in some human pathological states associated with CR [1].…”

Section: Discussionmentioning

confidence: 99%

“…Supporting this view are the ability of antisera raised against somatostatin (SS) to increase basal GH levels [3,4] and potentiate the GH response to GHRH [4], and the competence of TRH to elicit a paradoxical GH rise in the early postnatal period of the rat [5], or in some human central nervous system (CNS) dysfunctions [ 1], where the existence of a defective somatostatinergic func tion may be envisaged [ 1 ].…”

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confidence: 99%

Studies of Growth Hormone Secretion in Calorically Restricted Dogs: Effect of Cholinergic Agonists and Antagonists, Glucose and Thyrotropin-Releasing Hormone

Arce¹,

Cella²,

Locatelli³

et al. 1991

Neuroendocrinology

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The effect of caloric restriction (CR) on the growth hormone (GH) response to compounds reportedly capable of acting via somatostatinergic influences, i.e. cholinergic agonist or antagonist drug, glucose or thyrotropin-releasing hormone (TRH), administered alone or combined with GH-releasing hormone (GHRH), was evaluated in dogs. Eight beagle dogs, aged 4–5 years, underwent a 26-day period of increasing CR; they were evaluated either under basal conditions or starting from day 13 of CR, according to a schedule which allowed the mean length of CR to be similar among individual tests. CR resulted in a significant increase in basal GH levels, and starting from day 13 in a significant decrease in plasma somatomedin C levels; plasma glucose levels were significantly diminished on day 13 of CR and then remained unaltered. Administration of GHRH (GHRH1–44, 2 µg/kg, i.v.) induced a rise in plasma GH levels strikingly higher during CR than under basal conditions. Pyridostigmine (2 mg/kg orally), a muscarinic cholinergic agonist reportedly capable of restraining hypothalamic release of somatostatin (SS), enhanced the GH response to GHRH under basal conditions, but failed to do so during CR. Conversely, pirenzepine (0.6 mg/kg, i.v.), a muscarinic cholinergic antagonist, abolished the GHRH-induced GH rise under basal conditions, but only reduced it during CR. Only by doubling the dose of pirenzepine was complete inhibition of the GHRH-induced GH rise effected. Glucose alone (2 g/kg, p.o.) failed to modify basal GH secretion either before or during CR, but significantly inhibited the GHRH-induced GH rise either before or during CR. TRH (5 µg/kg, i.v.) did not modify plasma GH levels under basal conditions, but partially counteracted the rise in plasma GH occurring during CR. Like glucose, TRH significantly inhibited the GHRH-induced GH rise either before or during CR. Neither glucose nor TRH alone induced a ‘paradoxical’ rise in plasma GH during CR. In summary, (1) the data obtained with drugs affecting cholinergic transmission suggest that the latter is increased in dogs during CR and this likely results in a reduced hypothalamic SS tone, and (2) the data obtained with glucose and TRH suggest that these compounds may be effective to trigger not only hypothalamic SS release but also synthesis or, alternatively, they may act via inhibitory influences other than SS.

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Nonspecific Pituitary Responses to Hypothalamic Hormones in Basic and Clinical Research

Cited by 11 publications

References 166 publications

Growth Hormone Hyperresponsiveness to Growth Hormone‐releasing Hormone in Patients With Severe Liver Cirrhosis

Growth Hormone Hyperresponsiveness to Growth Hormone‐releasing Hormone in Patients With Severe Liver Cirrhosis

Differential abilities of the chicken Pit‐1 isoforms to regulate the chicken growth hormone promoter

Studies of Growth Hormone Secretion in Calorically Restricted Dogs: Effect of Cholinergic Agonists and Antagonists, Glucose and Thyrotropin-Releasing Hormone

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