Responsiveness of irradiated rat anterior pituitary cells to hypothalamic releasing hormones is restored by treatment with growth hormone.
Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation. Treatment with GH resulted in increased cell survival, which reached its maximum at the concentration of 5 nM, with an EC(50) of 3.5 nM. Protective effects of GH on pituitary cells were more pronounced in cultures treated before and after irradiation. Similarly, beneficial effects of GH were observed on the secretory capacity of surviving cells. In fact, irradiated pituitary cells treated with GH secreted substantial amounts of GH, luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone and adrenocorticotropic hormone in response to specific releasing hormones. Such effects of GH were prevented in the presence of the specific GH receptor antagonists B2036 and G120K. Our results show that r-hGH exerts a specific protective effect on irradiated rat pituitary cells and suggest possible use of GH as an adjuvant agent for prevention of postirradiation hypopituitarism.
Chiarenza
A
A
Department of Experimental and Clinical Pharmacology, University of Catania, School of Medicine, Catania, Italy.
Lempereur
L
L
Palmucci
T
T
Cantarella
G
G
Amico-Roxas
M
M
Goffin
V
V
Murabito
P
P
Magro
G
G
Bernardini
R
R
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives; D007018:Hypopituitarism / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
C119223:G120K-PEG; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D011092:Polyethylene Glycols; D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; C406545:pegvisomant