Changes in circulating levels of miR-30b during minipuberty and puberty in girls.

Context: Pubertal timing is tightly controlled by the hypothalamic-pituitary-gonadal (HPG) axis. Makorin RING finger protein 3 (MKRN3) is an inhibitor of the HPG axis and microRNA-30b (miR-30b) is proposed to act as a direct regulator of hypothalamic MKRN3 expression. Similarly, microRNA-155 (miR-155) targets CEBPB, which is also suggested to be involved in the activation of the HPG axis. Changes in circulating levels of both miRNAs have been observed in peripubertal boys but have not been studied in girls.

Objective: To investigate circulating levels of miR-30b-5p and miR-155-5p in healthy girls throughout minipuberty and puberty.

Methods: Longitudinal study of 18 female infants from the COPENHAGEN Minipuberty Study with serum samples during and after minipuberty and 29 girls from the Copenhagen Puberty Study with serum samples at pre-, peri-, and late puberty. miR-30b-5p and miR-155-5p were measured in serum by reverse transcription-qPCR using two different methods.

Results: Circulating miR-30b-5p levels decreased significantly after cessation of minipuberty (p<0.05), along with lower phosphorylation levels, suggesting decreased bioactivity. A significant increase in circulating levels of miR-30b-5p was observed at late puberty compared with pre- and peri-puberty (p<0.01). Additionally, a larger proportion of miR-30b-5p appeared to be phosphorylated in late puberty, suggesting increased bioactivity. Also, miR-155-5p showed a significant increase in late puberty compared with pre- and peri-puberty (p<0.01).

Conclusion: Circulating miR-30b-5p levels and its bioactivity followed the activity of the HPG axis during minipuberty and puberty, and miR-155-5p levels showed a similar pattern during puberty, suggesting regulatory roles on the HPG axis in girls.