What is the Origin of GHRH Resistance?

The term is derived from the molecular and clinical understanding of the Hypothalamic-Pituitary-Somatotropic axis. Resistance implies a failure at the receptor or post-receptor level on the target cell, which is the somatotroph in the anterior pituitary. This condition can be genetic, due to mutations in the GHRH receptor, or acquired, often secondary to chronic inflammation or obesity.

What is the Mechanism of GHRH Resistance?

GHRH resistance involves a defect in the signaling cascade initiated by GHRH binding to its receptor on the somatotroph cell membrane. In acquired cases, chronic exposure to high levels of inflammatory cytokines or elevated somatostatin tone can downregulate GHRH receptor expression or impair intracellular signaling pathways. The pituitary gland is physically present but functionally impaired in its ability to translate the GHRH signal into a robust pulsatile release of Growth Hormone.

GHRH Resistance

Meaning

A pathological state where the pituitary gland’s somatotroph cells exhibit a diminished or absent response to the stimulatory effects of Growth Hormone-Releasing Hormone (GHRH). This insensitivity results in inadequate secretion of Growth Hormone (GH), despite the hypothalamus producing and releasing sufficient amounts of GHRH. It represents a specific form of central growth hormone deficiency.