GHRH excess and blockade in X-LAG syndrome
X-linked acrogigantism (X-LAG) syndrome is a recently described, inheritable form of pituitary gigantism, resulting from micro-duplication on chromosome Xq26.3, including GPR101. The aetiology of X-LAG includes onset in early childhood and markedly high growth hormone (GH) and prolactin secreted from mixed pituitary hyperplasia/adenomas. The nature of X-LAG syndrome makes it challenging to control growth, even when employing multiple treatment modalities.
Daly et al. aimed to decipher the mechanism(s) driving hyperplasia, adenoma formation and secretory behaviour in vitro, using primary pituitary cell culture of an adenoma obtained from a female patient with X-LAG syndrome. GH-releasing hormone (GHRH), GH and prolactin were detected in primary pituitary adenoma cell-conditioned media. The GPR101 agonist GHRH1–5 had marginal effects on GH secretion, but no effect on prolactin release. Treatment with a GHRH receptor antagonist inhibited both GH and prolactin secretion, reversible by incubation with GHRH.
This study suggests that the GHRH pathway may be an important therapeutic target for controlling the hormonal secretion observed in X-LAG syndrome.
Read the full article in Endocrine-Related Cancer 23 161–170