Effects of porcine growth hormone on pregnancy and fetal/neonatal development in the rat.
Porcine growth hormone was given subcutaneously twice daily to two groups of 20 females at dose levels of 0.5 and 2.5 IU/kg (1 and 5 IU/kg/day). A control group of 20 females was similarly treated with vehicle. The females were given either vehicle or porcine growth hormone from gestation day (GD) 6 through GD 21, for 10 females that were cesarean sectioned, or through lactation day (LD) 21, for 10 females scheduled for natural delivery. There were no deaths, abortions, or drug-related physical signs in any treatment group. Drug-related effects during gestation were limited to significant (p < or = 0.05) pharmacologically mediated increases in F0 maternal body weight gain during GD 6-20 in the 2.5-IU/kg group, approximately 24% above controls. During LD 0-21, there were significant (p < or = 0.05) dose-related increases in average maternal body weight gain in the 0.5- and 2.5IU/kg groups (72 and 200% above controls, respectively). Consistent with these findings, there were dose-dependent increases in maternal serum growth hormone and IGF-1 levels noted on GD 21 and LD 21 in both drug-treated groups. There were no drug-related effects on embryonal/fetal survival, GD 21 fetal body weight, placental weight, fetal femur length and width, or fetal morphology as determined by external, visceral, and skeletal examinations. There were no drug-related effects on F1 pup mortality, physical signs, body weight, biparietal diameter, liver weight, and femur length or width. These data suggest that subcutaneous administration of growth hormone to pregnant and lactating rats, at a dose that produces significant (p < or = 0.05) increases in maternal body weight gain and serum IGF-1 levels, has no apparent effect on embryonal/fetal development or preweaning growth.
Spence
S
S
Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA.
Mattson
B
B
Vetter
C
C
Cukierski
M
M
Prahalada
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013552:Swine
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone