Pulsatile nyctohemeral and entropic modes of GH secretion after Estradiol (E2), GHRP-2 or the combination in post-menopausal women

To determine the impact of E2 on GHRP-2 actions, 10 postmenopausal women underwent 24h infusions of saline or GHRP-2 (1 μg/kg/h) after 7-12 days of placebo or oral micronized E2 (1 mg BID). GH profiles (every 10 min) were analyzed by deconvolution, cosinor fitting of 24h rhythms, and approximate entropy to quantitate the orderliness of GH release. GHRP-2 stimulated basal GH secretion 5-fold and GH secretory burst mass 8-fold without a change in the GH pulse frequency and increased the mean and 24h integrated serum GH concentrations (5.2 and 7.7 fold) as well as the 24h pulsatile and total daily GH secretion rate (8.4 and 7.9 fold). Also the disorderliness of GH secretion and the cosine amplitude (5 fold) were increased while the acrophase was advanced. E2 with GHRP-2 amplified the 24h rhythm 11-fold above basal (2-fold above GHRP-2 alone) and restored its acrophase to normal, as well as increased the disorderliness (higher approximate entrophy) of the 24h GH release process without enhancing further the GHRP-2 stimulated mean, 24h integrated serum GH or IGF-I concentrations. Additionally, the basal GH secretion, mass of GH secreted/burst GH pulse duration, frequency or half-life were unaltered by E2. GHRP-2 did not stimulate PRL or cortisol release with or without E2 replacement but did significantly raise serum IGF-I with and without E2. In conclusion: 1) E2 and GHRP-2 can interact to modulate the 24h rhythmicity of GH secretion; 2) the multifaceted dynamic responses to GHRP-2 and estradiol combined resemble the normal pubertal activation of the somatotropic axis; 3) these GH effects may reflect in part the GH releasing activity of the yet to be isolated putative GHRP-like natural ligand.