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Using preproghrelin-deficient mice ( Ghrl-/- ), we previously observed that preproghrelin modulates pulsatile growth hormone (GH) secretion in post-pubertal male mice. However, the role of ghrelin and its derived peptides in the regulation of growth parameters or feeding in females is unknown. We measured pulsatile GH secretion, growth, metabolic parameters and feeding behavior in adult  Ghrl-/-  and  Ghrl+/+  male and female mice. We also assessed GH release from pituitary explants and hypothalamic growth hormone-releasing hormone (GHRH) expression and immunoreactivity. Body weight and body fat mass, linear growth, spontaneous food intake and food intake following a 48-h fast, GH pituitary contents and GH release from pituitary explants  ex vivo , fasting glucose and glucose tolerance were not different among adult  Ghrl-/-  and  Ghrl+/+  male or female mice.  In vivo , pulsatile GH secretion was decreased, while approximate entropy, that quantified orderliness of secretion, was increased in adult  Ghrl-/-  females only, defining more irregular GH pattern. The number of neurons immunoreactive for GHRH visualized in the hypothalamic arcuate nucleus was increased in adult  Ghrl-/-  females, as compared to  Ghrl+/+  females, whereas the expression of GHRH was not different amongst groups. Thus, these results point to sex-specific effects of preproghrelin gene deletion on pulsatile GH secretion, but not feeding, growth or metabolic parameters, in adult mice.

Ghrelin Gene Deletion Alters Pulsatile Growth Hormone Secretion in Adult Female Mice