Sex-specific changes in postnatal GH and PRL secretion in somatotrope LEPR-null mice.

The developing pituitary is a rapidly changing environment that is constantly meeting the physiological demands of the growing organism. During early postnatal development, the anterior pituitary is refining patterns of anterior hormone secretion in response to numerous genetic factors. Our laboratory previously developed a somatotrope leptin receptor (LEPR) deletion mouse model that had decreased lean body mass, disrupted metabolism, decreased GH stores and was GH deficient as an adult. To understand how deletion of LEPR in somatotropes altered GH, we turned our attention to postnatal development. The current study examines GH, PRL, TSH, ACTH, LH and FSH secretion during postnatal days 4, 5, 8, 10 and 15 and compares age and sex differences. The LEPR mutants have dysregulation of GH ( P  < 0.03) and a reduced developmental prolactin peak in males ( P  < 0.04) and females ( P  < 0.002). There were no differences in weight between groups, and the postnatal leptin surge appeared to be normal. Percentages of immunolabeled GH cells were reduced in mutants compared with controls in all age groups by 35-61% in males and 41-44% in females. In addition, we measured pituitary expression of pituitary transcription factors, POU1F1 and PROP1. POU1F1 was reduced in mutant females at PND 10 ( P  < 0.009) and PND 15 ( P  < 0.02) but increased in males at PND 10 ( P  < 0.01). PROP1 was unchanged in female mutants but showed developmental increases at PND 5 ( P  < 0.02) and PND 15 ( P  < 0.01). These studies show that the dysfunction caused by LEPR deletion in somatotropes begins as early as neonatal development and involves developing GH and prolactin cells (somatolactotropes).