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Long-term effects on bone of postnatal immunization against GHRH in female and male rats
V Sibilia1, A E Rigamonti, F Pagani
1Department of Pharmacology, Chemotherapy and Medical Toxicology, Centre of Excellence of Neurodegenerative Diseases, University of Milan, Via Vanvitelli 32, Italy. Valeria.Sibilia@unimi.it
Insights
Neonatal passive immunization against growth hormone-releasing hormone (GHRH) impaired bone development in female rats, causing lower bone mineral density. Male rats showed no significant bone effects from this GHRH-Ab treatment.
Area of Science:
- Endocrinology
- Bone Biology
- Developmental Biology
Background:
- Growth hormone-releasing hormone (GHRH) plays a role in growth and development.
- The impact of neonatal GHRH manipulation on bone health, particularly sex differences, requires further investigation.
Purpose of the Study:
- To investigate the long-term effects of neonatal passive immunization against GHRH on bone mineral content and density in male and female rats.
- To assess the influence of GHRH antibody (GHRH-Ab) treatment on bone turnover markers and IGF-I levels.
Main Methods:
- Neonatal rats received subcutaneous GHRH-Ab from day 1 to 10.
- Bone mineral content (BMC) and bone mineral density (BMD) were measured monthly until 7 months.
- Urinary lysylpyridinoline (LP), serum osteocalcin (OC), and serum IGF-I were analyzed at specific time points.
Main Results:
- Female rats exhibited significantly lower whole body and femoral BMC and BMD from 2 to 7 months post-treatment.
- Female rats showed reduced IGF-I levels at 2 and 3 months, correlating with decreased bone growth.
- While both sexes had increased LP excretion, only males showed increased OC levels; females had no significant change in OC.
Conclusions:
- Transient neonatal GHRH deprivation induces an osteopenic effect specifically in female rats.
- Sex-dependent differences in bone response to neonatal GHRH manipulation were observed.
- These findings highlight the critical role of GHRH in female bone development during early life.
Abstract:
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.
