Session: SAT 596-621-Pediatric Endocrinology /Steroids and Puberty
Poster Board SAT-605
To examine how the Lin28/let-7 axis affects puberty in males and females and to investigate whether this regulation is let-7-dependent, we determined the timing of puberty in Lin28b-deficient mice and in let-7 overexpressing mice. Pubertal timing was assessed using preputial separation (PS) in males and vaginal opening (VO) in females.
Because Lin28a gain-of-function female mice have later VO, we expected Lin28b-deficient and let-7 overexpressing mice to have earlier puberty. Surprisingly, pubertal timing was unaffected in both Lin28b-deficient and let-7 gain-of-function (GOF) female mice. In contrast, Lin28b-deficient male mice as well as let-7 GOF male mice reached PS two days later than wildtype littermate controls (28.8 +/- 2.4 vs 26.9 +/- 1.8 for Lin28b-/- and 28.4 +/- 2.0 vs 26.1 +/- 1.4 for let-7 GOF, respectively; p<0.01 for both strains). The delayed puberty cannot be explained by delayed growth; the let-7 GOF male mice were larger than controls at puberty (p<0.05). The sex-specific phenotypes were observed despite evidence that Lin28b was knocked out and that increased levels of mature let-7miRNA were present in both sexes.
Combined, our data strongly suggest that the Lin28/let-7 pathway regulates puberty in a sex-specific manner. In addition, Lin28b may regulate puberty more robustly in males than in females, and regulation of female puberty may, in part, be let-7 independent. These findings provide new opportunities to investigate how male and female puberty is differentially regulated.
Nothing to Disclose: CA, GS, HZ, DC, CC, GQD, MRP
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