Growth Hormone Response to Overnight Growth Hormone-Releasing Hormone Infusion and Oral Pyridostigmine in Children with Short Stature

Ross, R.J.M., Savage, M.O., Kirk, J.M.W. and Besser, G.M. (Departments of Endocrinology and Child Health, St Bartholomew's Hospital, London, UK). Growth hormone response to overnight growth hormone-releasing hormone infusion and oral pyridostigmine in children with short stature. Acta Paediatr Scand [Suppl] 349: 114, 1989.
The development of a long-acting or depot preparation of growth hormone-releasing hormone (GHRH) may have many advantages over conventional treatment (with GH) of GH-deficient children. Pyridostigmine, an acetylcholinesterase inhibitor, has been shown to augment basal GH secretion and the GH response to GHRH in short children. It may thus provide adjuvant therapy to depot GHRH. The GH response to a nocturnal subcutaneous infusion of GHRH (1–29)NH₂ in doses of 5 and 10 pg/kg/hour was investigated in five short, slowly growing children. The effect of oral pyridostigmine 60 mg on nocturnal GH secretion and the GH response to a nocturnal infusion was also examined. The subcutaneous infusion of GHRH augmented pulsatile GH release in all five children. There was a dose-related response to subcutaneous GHRH for the GH area under the curve and mean GH pulse amplitude, but no change in the number of pulses. There was a significant rise in the mean baseline GH concentration during the GHRH infusion compared with placebo. Pyridostigmine had no effect on either basal or stimulated GH secretion.     

Diagnostic Value of Growth Hormone-Releasing Hormone Tests in Short Children

Butenandt O. (Department of Paediatric Endocrinology, Children's Hospital, University of Munich, Munich, West Germany). Diagnostic value of growth hormone-releasing hormone tests in short children. Acta Paediatr Scand [Suppl] 349 93, 1989.
The growth hormone-releasing hormone (GHRH) test was applied to more than 230 children. Twenty-five out of 61 patients with proven growth hormone (GH) deficiency responded to GHRH with a GH increase of greater than 10 ng/ml. In most of the patients with idiopathic GH deficiency, a priming procedure using daily injections of GHRH improved the secretory response to GHRH. Nearly all children with familial shortness of stature showed a prompt increase in GH levels, with a mean peak level of 34.9 ng/ml (range 0.5–144 ng/ml). A second test was performed in five children with familial short stature because of failure to respond to the first test. Children with constitutional delay of growth and development did not differ in their GH response from patients with familial shortness of stature. Ten girls with Ullrich-Turner's syndrome responded with a mean increase of 22 ng/ml GH (range 10.1–34.0 nglml). Therapy with glucocorticoids, as well as endogenous hypersecretion of cortisol, suppressed the responsiveness of the pituitary gland to GHRH. Suppression was also observed following a single dose of dexamethasone during the steroid-suppression test in eight obese children. Low responsiveness of the pituitary gland was also seen in patients with thalassaemia and transfusion-induced haemosiderosis. It is concluded that it is not possible to detect GH deficiency with a single GHRH test. A full endo-crinological evaluation is necessary to prove the diagnosis.     

An Introduction to Molecular Biology: Gene Structure, Expression, and Mutation

This mini-review outlines DNA structure and the regulation of gene expression. It then discusses the nature of mutations, techniques employed to detect them, and the limitations of these techniques.     

Serum Binding Proteins for Growth Hormone: Origins, Regulation of Gene Expression and Possible Roles

The above discussion highlights the heterogeneity of the family of GH receptors/GHBPs and their mRNAs. Considerable uncertainty still exists as to the interrelationships between the various forms, the specific mechanisms for their generation and their possible significance in terms of modulating GH action and receptor function. Collectively, the regulatory data indicate that while the mRNAs encoding the membrane and soluble GH receptors/GHBPs in the rat are expressed by the same broad distribution of tissues, they can be differentially regulated. Such regulated expression implies a functional basis for production of GHBP. The wide tissue distribution of GHBP mRNA also suggests a role for GHBP as a paracrine/autocrine effector molecule, perhaps in addition to an endocrine role. Additional studies, both in vitro and in vivo , perhaps utilizing highly purified recombinant GHBP, will be required to provide more definitive information as to the true physiological role(s) of the circulating GHBPs.     

Response to Growth Hormone-Releasing Hormone as Evidence of Hypothalamic Defect in Optic Nerve Hypoplasia

ABSTRACT. Hypothalamic-pituitary function was studied in four children with Optic Nerve Hypoplasia (ONH). All were found to be growth hormone deficient when provoked with glucagon or insulin induced hypoglycaemia (ITT), but did respond to bolus injection of GHRH. This indicates a primary hypothalamic defect. Virtual absence of pituitary tissue on high resolution CT scan explained the poor response of one child. One child has shown an excellent response to treatment with subcutaneous GHRH, which is physiologically the most appropriate treatment for this condition.     

Expression and Physiological Significance of Growth Hormone Receptors and Growth Hormone Binding Proteins in Rat and Man

The molecular structure of the GH receptor has recently been characterized and the receptor identified as a member of a new receptor superfamily that includes the prolactin receptor and
several cytokine receptors. No obvious signal transducing domain has been identified on any of these related receptors. One possible signalling mechanism involves receptor interaction with other membrane-associated proteins that function as mediators of signal transduction. Whether such a mechanism is involved in signal transduction of the GH receptor is not known. Another common feature of these receptors is the presence of soluble forms such as the GHBP. The functions of these proteins in the circulation and at the level of the target cell remain to be resolved.     

Use of Continuous Subcutaneous Growth Hormone-Releasing Hormone (GHRH (1–29)NH2) Infusions to Augment Growth Hormone Secretion and to Promote Growth

Brain, C., Hindmarsh, P.C., Pringle, P.J. and Brook, C.G.D. (Endocrine Unit, the Middlesex Hospital, London, UK). Use of continuous subcutaneous growth hormone-releasing hormone (GHRH (1–29)NH₂) infusions to augment growth hormone secretion and to promote growth. Acta Paediatr Scand [Suppl] 349: 109, 1989.
It has previously been shown that an 8-day continuous subcutaneous infusion of GHRH (1–29)NH₂ in adult males augments growth hormone (GH) secretion with no evidence of desensitization of the response. The present report details the results of treatment with continuous subcutaneous infusions of CHRH (1–29)NH₂ in eight children aged 6–9 years with partial GH insufficiency. All the children showed augmentation of GH secretion and an increase in growth velocity after 3 and 6 months of therapy.     

Growth Hormone (GH-1) Gene Deletions in Children with Isolated Growth Hormone Deficiency (IGHD)

Objective  

To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile.     

Growth Hormone Response to Growth Hormone-Releasing Hormone (hp GHRH-1-44) as an Index of Growth Hormone Secretory Dysfunction after Prophylactic Cranial Irradiation for Acute Lymphoblastic Leukemia (24 Grays)

ABSTRACT. The growth hormone response to growth hormone releasing hormone hp GHRH_1-14 (2 μg/kg i.v.) was studied in 19 prepubertal children who had been irradiated with 24 Gy for acute lymphoblastic leukemia (ALL) or lymphosarcoma (LS) at a mean chronological age of 410/12 years (limits 10/12 to 9 years). They were evaluated after a mean time interval of 4 8/12±3/12 years and compared to 14 prepubertal children with constitutional short stature (CSS). The individual responses to GHRH were decreased in all but three of the irradiated children. The mean GH response was 16.7±2.5 ng/ml as compared to 52.6±8.5 ng/ml in the control group ( p <0.001). The GH response to GHRH was not correlated with the GH response to arginine-insulin tolerance test (AITT). A decreased response to GHRH with values between 12.5 and 19.4 ng/ml was observed in four cases with normal growth rates and normal GH responses to AITT. These results suggest that an impaired GH response to GHRH is a frequent finding after cranial irradiation for ALL or LS and may be the only sign of GH secretory dysfunction. It is probably indicative of early hypothalamic impairment of GH secretion.     

Modification of 24-Hour Growth Hormone Secretion after Continuous Subcutaneous Infusion of Growth Hormone-Releasing Hormone (GHRH (1–29)NH2) in Short Children with Low 24-Hour Growth Hormone Secretion

Tauber, M.T., Pienkowski, C., Landier, F., Gunnarsson, R. and Rochiccioli, P. (Department of Paediatric Endocrinology, CHU Rangueil, Toulouse Cedex, and Kabi Laboratory, Paris, France and Kabi Peptide Hormones, Stockholm, Sweden). Modification of 24-hour growth hormone secretion after continuous subcutaneous infusion of growth hormone-releasing hormone (GHRH (1–29)NH₂) in short children with low 24-hour growth hormone secretion. Acta Paediatr Scand [Suppl] 349: 117, 1989.
Six short children with low 24-hour growth hormone (GH) secretion were treated with continuous subcutaneous infusion of GHRH (1–29)NH₂ for 3 weeks using a portable infusion pump. Restoration of pulsatile GH secretion was observed in all three children treated with 40 pg/kg/day of GHRH, but in only one of the three children treated with 20 pg/kg/day. All parameters of 24-hour GH secretion increased, but in five children the magnitude of the GH response was greater on day 1 than on day 21 of CHRH treatment. This decrease was not observed in the single child who responded to a low dose of GHRH (20 pg/kg/day); on the contrary, the response in this patient was greater after 21 days of GHRH treatment. Plasma levels of GHRH (1–29)NH₂ were significantly higher on day 21 than on day 1 of treatment, suggesting altered pharmacokinetics over time. The effect of GHRH treatment on growth could not be determined because of the short duration of the study, but the data obtained on 24-hour GH secretion and GHRH metabolism suggest that a long-acting analogue of GHRH could be useful for the treatment of GH deficient or insufficient children.