Glycoprotein hormone alpha-subunit response to growth hormone (GH)-releasing hormone in patients with active acromegaly : evidence for alpha-subunit and GH coexistence in the same tumoral cell

Basal serum concentrations of glycoprotein hormone alpha-subunit and its response to GH-releasing hormone (GHRH) were studied in 22 acromegalic patients and in normal subjects. Four out of 22 patients had a basal alpha-subunit concentration (1.2-3.5 ng/ml) clearly above the upper limit of the normal range. GHRH injection (1 microgram/kg body weight, bolus dose iv) produced a clear alpha-subunit response [mean % increase: 120 +/- 37 (SD)] in the 4 patients with elevated basal alpha-subunit levels. No increase in serum glycoprotein hormones (TSH, LH, and FSH) occurred. Selective adenomectomy in 2 patients resulted in normalization of both serum GH and alpha-subunit levels, as well as disappearance of the abnormal alpha-subunit response to GHRH. In in vitro studies, only these 2 adenomas secreted alpha-subunit in large amounts (534 and 388 ng/mg protein . 30 min) and was it further stimulated by GHRH (% increase: 83 and 126). Morphological studies done with protein A-gold particle immunotechnique demonstrated that in these adenomas the great majority of the cells contained secretory granules positive for both GH and alpha-subunit. We conclude that: 1) alpha-subunit hypersecretion is present in some acromegalic patients (about 20%), 2) GHRH stimulates alpha-subunit release both in vivo and in vitro only in patients with elevated basal alpha-subunit levels, and 3) in these patients alpha-subunit derives from a common adenomatous cell secreting both alpha-subunit and GH molecules.