Growth hormone/insulin-like growth factor-1 response to acute and chronic growth hormone-releasing peptide-2, growth hormone-releasing hormone 1-44NH2 and in combination in older men and women with decreased growth hormone secretion.

To better appreciate the interactions of GHRP-2 and GHRH 1-44NH2 on the release of GH in normal adult men and women with decreased GH secretion and low serum IGF-1 levels, a series of acute and chronic studies have been performed (n = 5 men, 5 women). The acute iv bolus GH responses of these subjects to the two peptides alone and together suggest that the decreased GH secretion may be primarily due to a deficiency of the natural endogenous GHRP, ghrelin, rather than a decreased secretion of endogenous GHRH or excess secretion of SRIF. To determine whether the low GH response to GHRH was due to a limited capacity of pituitary to release GH, higher dosages of GHRP-2 alone were administered. At a dose of 1 microg/kg GHRP-2 the GH response was essentially the same as that elicited by 1 microg/kg GHRH + 0.1 microg/kg GHRP-2 while the GH response to 10 microg/kg GHRP-2 sc was about twice as high in both men and women. Although these subjects have a limited pituitary capacity to release GH, which is also an indication of decreased GH secretion in the presence of low serum IGF-1 levels, this alone would not explain the low GH response to GHRH. Furthermore, the finding that a low dose of 0.1 microg/kg GHRP-2 augments the GH response to 1 microg/kg GHRH is strongly against an excess secretion of SRIF. Twenty-four hour profiles of GH secretion during placebo, GHRP-2, and various doses of GHRH alone and together with GHRP-2 were studied. In addition, 1 microg/kg/h GHRP-2 was infused continuously sc to these subjects for 30 d. The normal pulsatile secretion of GH as well as the serum IGF-1 level was increased after 24 h and remained elevated for 30 d. With a deficiency of endogenous GHRH, the GH response of GHRP-2 would be little to none, while in subjects with a deficiency of the natural GHRP, the GH response to GHRH would be more attenuated. Thus, in chronic deficiency the GH response would be expected to depend on the degree of the capacity of the pituitary to release GH as well as the type(s) of hormonal deficiency.

Nonhypoglycemic effects of thiazolidinediones.

The thiazolidinediones are a new class of compounds for treatment of type 2 diabetes. Troglitazone became available in the United States in 1997 but was withdrawn from the market in March 2000 because it caused severe idiosyncratic liver injury. Rosiglitazone and pioglitazone have been available since 1999. Because these drugs directly improve insulin resistance and decrease plasma insulin levels (a risk factor for coronary artery disease), they may decrease risk for cardiovascular disease in patients with type 2 diabetes. Research on the non-glucose lowering effects of troglitazone and, to a lesser extent, of rosiglitazone and pioglitazone have demonstrated changes in several cardiovascular risk factors associated with the insulin resistance syndrome. These beneficial effects include a decrease in blood pressure, correction of diabetic dyslipidemia, improvement of fibrinolysis, and decrease in carotid artery intima-media thickness. Other in vitro effects related to the ability of these agents to bind a newly described class of receptors (peroxisome proliferator-activated receptors) may also have implications for atherosclerosis. However, these drugs increase low-density lipoprotein (LDL) cholesterol levels and may favorably change LDL particle size and susceptibility to oxidation (although the implications of the latter changes are not dear). Furthermore, these drugs tend to cause weight gain. The authors' enthusiasm for these drugs has diminished somewhat because of reported adverse events, including rare liver failure. Nevertheless, because of the mechanism of action of the thiazolidinediones, clinical trials designed to determine whether they (or similar "insulin sensitizers") decrease cardiovascular events in people with type 2 diabetes will be of interest.

GHRP-2, GHRH and SRIF interrelationships during chronic administration of GHRP-2 to humans.

Studies with chronic GHRP-2 or GHRH administration were performed to demonstrate and better understand the interrelationships between GHRP-2, GHRH and SRIF. Normal younger and older men and women received chronic GHRP-2, GHRH or GHRP-2 + GHRH for 7-30 days. It was demonstrated that chronic administration of either GHRP-2 or GHRH could convert an additive GHRP-2 + GHRH GH response to a synergistic one. In addition, the type of synergistic response induced by chronic GHRP-2 versus GHRH was different. Whether the GH response becomes desensitized during chronic administration depends in part on the dosage and frequency of administration. The potential to learn more about the in vivo actions of GHRP relative to the regulation of GH secretion is underscored by studying the GH responses to GHRP-2, GHRH and GHRP-2 + GHRH.