The effects of neonatal passive immunization against GHRH on bone was examined in male and female rats. Pups were treated subcutaneously with GHRH-antiserum (GHRH-Ab) from day 1 to day 10 of age. Bone mineral content (BMC) and bone mineral density (BMD) were evaluated at monthly intervals until 7 months. Markers of bone resorption (urinary lysylpyridinoline, LP), bone formation (serum osteocalcin, OC) and serum IGF-I were measured at 2, 3 and 7 months. In male rats, GHRH-Ab did not modify BMC and BMD when compared with controls. In contrast, female rats demonstrated lower whole body and femoral BMC and BMD from 2 to 7 months of age. Reduced bone growth in the females was associated with lower IGF-I levels than controls at 2 and 3 months of age, whereas in males IGF-I titers did not change during the period of the study. LP excretion was higher in GHRH-Ab-treated rats at 2 and 3 months in both sexes. In females, no difference in OC values was recorded, whereas in GHRH-Ab-treated males, there was an increase in OC levels at 2 and 3 months. These data indicate that transient GHRH deprivation induces an osteopenic effect in female rats which is not evident in male rats.
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V Sibilia, AE Rigamonti, F Pagani, N Lattuada, F Guidobono, WB Wehrenberg, EE Muller, and C Netti
R Grilli, V Sibilia, A Torsello, F Pagani, M Guidi, M Luoni, C Netti, and E E Müller
To study possible age-related differences in the role of neuronal histaminergic pathways in the control of GH secretion, the effects of α-fluoromethylhistidine (α-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection of α-FMH (20 mg/kg, s.c.) in pups of either sex, from birth until 10 days of age, caused a significant increase in baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin analog FK 33–824 (1 mg/kg, s.c.) administered 3 h after the last α-FMH injection. GH and SRIF mRNA levels were significantly higher in α-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of α-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33–824 (0·3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of α-FMH (200 μg/rat, i.c.v., for 3 days) failed to modify basal and FK 33–824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged.
These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.
Journal of Endocrinology (1996) 151, 195–201