Sex differences in the endocrine system in response to protein intake early in life.

Background: Nutritional factors during a sensitive period can influence child development in a sex-related manner.

Objective: Our aim was to investigate whether sex modulates the responses of relevant biochemical parameters and growth to different protein intakes early in life.

Design: In a randomized controlled trial, formula-fed infants were assigned to receive formula with higher protein (HP) or lower protein (LP) content. The main outcome measures were insulin-like growth factor (IGF)-1 axis parameters, weight, length, BMI, leptin, and C-peptide/creatinine ratio at 6 mo of age. Dietary intake during the first 6 mo of life was also assessed.

Results: The IGF-1 axis response to HP feeding was modulated by sex. Total and free IGF-1 and IGF binding protein 3 concentrations were higher in girls than in boys. Compared with the LP diet, the HP diet was associated with higher IGF-1 and lower IGF binding protein 2 secretion. The response to this HP content formula tended to be stronger in girls than in boys. The HP diet was associated with a higher C-peptide/creatinine ratio. The leptin concentration was higher in girls than in boys and was correlated to the IGF-1 axis parameters. No interaction between sex and nutritional intervention was shown on growth.

Conclusions: Our findings show that the endocrine response to a high protein diet early in life may be modulated by sex. The IGF-1 axis of female infants shows a stronger response to the nutritional intervention than does that of male infants, but there is no enhanced effect on growth. This trial was registered at clinicaltrials.gov as NCT00338689.