GROWTH-HORMONE (GH) DEPRIVATION-INDUCED BY PASSIVE-IMMUNIZATION AGAINST RAT GH-RELEASING FACTOR DOES NOT DISTURB THE COURSE OF SEXUAL-MATURATION AND FERTILITY IN THE FEMALE RAT

The importance of normal GH secretion for the onset of sexual maturati on is a subject of controversy. Also, the need to achieve a minimal bo dy size or body fat content has been postulated to be of importance fo r determining the timing of the onset of puberty. To evaluate the impo rtance of GH secretion on the onset of sexual maturation in the female rat, GH deprivation has been induced by treating prepubertal rats wit h antirat GRF serum to passively immunize these animals against GRF. C hronic administration of anti-GRF serum produced in all series an impr essive reduction in growth rate (from 5 to 2 g/day), resulting in a bo dy weight averaging 50-60% the normal value at 50 days of life. Despit e this deficit in growth, sexual maturation, as established by vaginal opening and first estrous cycles, occurred at the normal age in three of four series of rats; in one series, however, sexual maturation was delayed by 4 days, but thereafter, all parameters indicated that the gonadotropic axis was normally activated. In one series, fertility was tested at 59 days of age in females with a body weight corresponding to 51% of the control weight; these females conceived and delivered a reduced number of pups (9.4 +/- 0.7 instead of 14.2 +/- 0.8 in control dams), but the pups were of normal size. In a second experimental app roach, the effect of GH deprivation was evaluated in a model of late s exual maturation obtained by severe food restriction followed by a swi tch to ad libitum feeding. Severe food restriction initiated at approx imately 28 days, when the body weight was 75 g, drastically reduced th e growth rate and completely prevented sexual maturation. A switch to ad libitum feeding at 50 days provoked an important compensatory growt h and the occurrence of sexual maturation 4 days later. Passive immuni zation against GRF during this recovery phase did reduce the growth ra te, but did not delay sexual maturation. Plasma insulin-like growth fa ctor-I (IGF-I) secretion was very low in food-restricted rats and in e ach situation with induced GH deprivation. During food restriction, pl asma IGF-binding protein-3 (IGFBP-3) and to a lesser extent IGFBP-1 we re decreased, and IGFBP-2 was increased; after switching to ad libitum feeding, plasma levels of IGFBP-2 normalized, but levels of IGFBP-1 a nd IGFBP-3 remained low in the face of normalized plasma IGF-I levels. In summary, GH deficiency induced by passive immunization against GRF drastically reduced growth and food intake, but did not significantly delay sexual maturation in female rats. Severe food restriction delay ed sexual maturation, but when food restriction was terminated, impose d GH deprivation did not prevent the accelerated sexual maturation tha t takes place in these conditions. It is noteworthy that in GH-deprive d rats, sexual maturation was normal in the presence of markedly reduc ed circulating plasma IGF-I levels. It is concluded that in the female rat, normal GH and/or IGF-I secretion is not required for sexual matu ration to occur, and that this developmental step can take place at ve ry different body weights and growth rates. Thus, metabolic parameters other than GH or IGF-I are responsible for the delay in sexual matura tion in situations of malnutrition.