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.
P
P
Beck-Peccoz
M
M
Bassetti
A
A
Spada
G
G
Medri
M
M
Arosio
G
G
Giannattasio
G
G
Faglia
D000172:Acromegaly / Q000097:blood / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism* / Q000648:ultrastructure; D000328:Adult; D000368:Aged; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015292:Glycoprotein Hormones, alpha Subunit; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000097:blood / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D011863:Radioimmunoassay; D013972:Thyrotropin / Q000097:blood
D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone