Somatotropic dysfunction in growth hormone-releasing hormone-deprived neonatal rats: effect of growth hormone replacement therapy.
In a previous work, we reported that passive immunization with anti-growth hormone-releasing hormone (GHRH) antibodies (GHRH-Ab) in neonatal rats caused disruption of somatotropic function that was still present 60 d posttreatment. We studied the reversibility of this condition by growth hormone (GH) replacement therapy. Neonatal rats received GHRH-Ab (50 microL/rat, s.c.) or normal rabbit serum every second day from birth up to postnatal d 10 and received hGH (0.4 microgram/g body weight, s.c., b.i.d.) or vehicle in a 2 x 2 factorial design. Animals were studied on d 11 of age. In GHRH-Ab-treated rats, GH therapy 1) counteracted the reduced body weight and low plasma IGF-I levels; 2) failed to modify the reduced pituitary weight and GH content; 3) further reduced the low plasma GH levels; 4) partially restored the defective GH responsiveness to GHRH; 5) failed to modify the reduced hypothalamic somatostatin and increased GHRH gene expression in the hypothalamus; and 6) reverted the decreased pituitary somatostatin binding. Morphologic and morphometric evaluation of the pituitary gland from GHRH-AB+GH pups showed that the number of GH-labeled structures was lower than in normal rat serum-GH-treated pups, whereas the total GH immunoreactivity per unit surface, an index of intracellular hormone concentration, was slightly higher than in vehicle-GH or GHRH-Ab pups. As determined by electron microscopy, somatotropes from GHRH-Ab+GH pups had morphologic features of high cellular activity. It appears that in GHRH-deprived pups GH replacement therapy can normalize most but not all altered indices of the somatotropic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Cella
S G
SG
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
De Gennaro Colonna
V
V
Locatelli
V
V
Bestetti
G E
GE
Rossi
G L
GL
Torsello
A
A
Wehrenberg
W B
WB
Müller
E E
EE
D000818:Animals; D000831:Animals, Newborn; D003720:Densitometry; D005069:Evaluation Studies as Topic; D015870:Gene Expression; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D013007:Growth Hormone-Releasing Hormone / Q000172:deficiency*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone