Growth hormone secretagogues and hypothalamic networks

Area of Science:

• Neuroendocrinology
• Hormone Regulation
• Molecular Endocrinology

Background:

• Growth hormone secretagogues (GHSs) are known to stimulate growth hormone (GH) secretion.
• Their actions involve complex regulatory pathways at both pituitary and hypothalamic levels.
• Previous understanding of GHSs' hypothalamic actions was limited.

Purpose of the Study:

• To elucidate the complex mechanisms underlying GHS actions on GH secretion at the hypothalamic level.
• To investigate the role of GHS receptors and their coexpression with key hypothalamic neurons.
• To understand the dual effects of GHSs, including paradoxical inhibition of GH secretion.

Main Methods:

• Utilized antisense strategy to investigate the role of somatostatin (SST) in activating arcuate GHRH neurons.
• Examined GHS receptor distribution and coexpression with GHRH, somatostatin, and neuropeptide Y (NPY) neurons.
• Investigated the differential effects of stimulating distinct NPY neuron populations on GH secretion.

Main Results:

• GHSs reinforce GHRH-induced GH secretion at the pituitary by mobilizing intracellular calcium.
• Chronic GHS treatment leads to reduced responsiveness, likely due to negative feedback on GHRH release.
• GHS receptors are widespread and coexpressed by GHRH, somatostatin, and NPY neurons.
• GHSs can activate GHRH neurons directly or indirectly, potentially via somatostatin interneurons.
• Distinct NPY neuron populations stimulated by GHSs exert opposing effects on GH secretion, with some facilitating GHRH release and others activating somatostatin release.

Conclusions:

• GHS actions on GH secretion are complex and multifaceted, particularly at the hypothalamic level.
• GHSs modulate GH secretion through intricate interactions with GHRH, somatostatin, and NPY neuronal systems.
• The dual effects of GHSs, including potential inhibition, are mediated by differential activation of specific neuronal pathways within the hypothalamus.