Loss of Somatotrope Leptin Receptors Reduces Neonatal Expression of PROP1 and POU1F1 and the Postnatal Leptin Surge in Females
Presentation Number: SAT 437
Date of Presentation: April 1st, 2017
Melody Lyn Allensworth*, Angela K. Odle, Anessa C. Haney, Andrea Melgar Castillo, Angus M. MacNicol and Gwen V. Childs
University of Arkansas for Medical Sciences, Little Rock, AR
Prophet of Pit1 (Prop1) is maximally expressed on embryonic day 12.5 and leads to expression of the transcription factor Pou1f1/ Pit1 that forms the Pit1-dependent lineage of the pituitary: the thyrotropes, lactotropes, and somatotropes. Mutations in Prop1 and Pit1 can lead to numerous endocrine disorders. Previously in our lab, we selectively knocked out leptin receptors (LEPR) in somatotropes using CreLox. These Lepr-null mice show adult-onset GH deficiency and sex-specific changes in postnatal serum levels of TSH, PRL, and GH. Mutant male pups are GH deficient by postnatal day (PND) 21 while females become GH deficient in adulthood. Lepr-null females also have a blunted rise in TSH (20%) and PRL (77%) serum levels between PND 5 and 15. These changes led to the hypothesis that leptin may be required for the expansion of the Pit-1 lineage. We previously reported significant reductions in PIT1 immunolabeled cells in Lepr-null adult animals.
In this current study, we collected pituitaries from Lepr-null and littermate control mice at PND 5, 10, 15 for assays of PIT1 and PROP1 protein content (MyBiosource.com). In controls, PIT1 levels (ng/μg protein) rose to a peak on PND 10 from 161±49 ng (females) or 123±24 ng (males) to 291±169 ng (females) or 259±123 ng (males) followed by an 80-85% decline at PND 15 (ANOVA, Neuman-Keuls p<0.04). In contrast, in somatotrope Lepr-null mutants, PIT1 levels did not rise and were 54-71% (males) or 48-60% (females) lower than PND 5-10 controls. Control and mutant males had a normal leptin surge with a peak at PND 10 that correlated with peak PIT1 levels. In contrast, mutant females showed no leptin surge at PND 10 (p<.01), which may correlate with lower serum TSH or PRL in females as both of these hormones have been reported to stimulate adipocyte leptin.
PROP1 content levels were also assayed to determine if the above changes reflected the fact that it was also a leptin target. Our assays of control PROP1 levels confirm studies by Perez Milan, showing high PROP1 levels in neonatal males and females. However, our assays of PND 10 Lepr-null males and females showed that PROP1 was reduced by 37% (p<.01) and 48% (p<.04) respectively as compared to controls.
These studies help explain our previous findings showing that leptin may be needed for full secretion of TSH and PRL in the neonatal female and normal GH in the adult. The current studies show that PROP1 and PIT1 are targets for leptin during neonatal development. This discovery may thus signify a role for leptin in the expression of the progenitor cell transcription factors needed for the expansion of the PIT1 cell lineage.
Nothing to Disclose: MLA, AKO, ACH, AM, AMM, GVC