LONG-TERM CHANGES OF SOMATOTROPIC FUNCTION INDUCED BY DEPRIVATION OF GROWTH HORMONE-RELEASING HORMONE DURING THE FETAL LIFE OF THE RAT

We have studied the effects of intra-amniotic administration of an ant i-GH-releasing hormone serum (GHRH-Ab) on day 16 of fetal life in the rat, when the ontogenetic development of the GHRH neuronal system occu rs. Control animals received normal rabbit serum. Following delivery, body weight was monitored for the next 30 days as an index of somatic growth, and the following indices of somatotrophic function were deter mined: plasma and pituitary GH, pituitary GH mRNA, hypothalamic GHRH a nd somatostatin mRNA, and the in vivo GH responsiveness to GHRH. At bi rth, GHRH-Ab-treated rats had a body weight that was equivalent to tha t of control rats but, starting from postnatal day 6 up to day 30, the y had a significantly reduced body weight. Pituitary weight, the absol ute pituitary GH content and GH mRNA levels were lower in experimental compared with control rats, while pituitary GH concentrations were si milar in the two groups, thus implying that there was a defect, not on ly in GH synthesis, but also in GH release. In agreement with this the ory, basal GH levels and GHRH-stimulated GH secretion were reduced in GHRH-Ab-treated rats but, in contrast, hypothalamic regulation of GH s ecretion appeared to be working in these rats as they were still able to respond to the low plasma GH by increasing GHRH and decreasing soma tostatin mRNA levels. These findings indicate that deprivation of GHRH during fetal life induces long-lasting changes of growth rate and som atotrophic function. In addition, when comparing these changes with th ose in rats given GHRH-Ab postnatally, it would appear that deprivatio n of GHRH affects different regulatory levels of the hypothalamo-pitui tary-somatotroph axis depending on when the deprivation occurs.