Endocrine Abstracts

JOINT1028

Background: Puberty is characterized by major physiological and psychological changes required for achieving sexual maturation and fertility. Pubertal timing is tightly controlled by the hypothalamic-pituitary-gonadal (HPG) axis, with the initiation of puberty driven by the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Makorin RING finger protein 3 (MKRN3), encoded by the maternally imprinted gene MKRN3, acts as an inhibitor to suppress GnRH activity and delay pubertal onset. MicroRNA-30b (miR-30b) has been proposed to act as a direct regulator of hypothalamic MKRN3 expression and circulating levels of miR-30b-5p increase in concert with a decrease in circulating levels of MKRN3 in pubertal boys. However, it has not been described whether this is also the case in girls.

Materials and Methods: Longitudinal serum samples from 18 female infants from The COPENHAGEN Minipuberty Study (median age 3.7 months and 8.4 months, representing peri- and post-minipuberty, respectively), 29 girls (Tanner stage B1, B2 and ≥ B3 representing prepuberty, peripuberty, and postpuberty, respectively), and 24 young women (median age 19.0 yrs, single sample) from The Copenhagen Puberty Study were included. Serum from 23 pregnant women from The Copenhagen Mother-Child Cohort (median age 29.9 yrs, single samples) were also included. miR-30b-5p was measured in serum by reverse transcription quantitative PCR. Additionally, miR-30-5p expression was assessed by miRNA in situ hybridization in ovarian tissue from eight adult women. Wilcoxon signed-rank test and Pearson’s correlation coefficient were used to analyze the data.

Results: Circulating miR-30b-5p levels decreased significantly from the peri- to the post-minipubertal stage (p = 0.048). A significant increase in circulating levels of miR-30b-5p was observed in girls at the post-pubertal stage compared with girls at the pre- and the peri-pubertal stages (p = 0.0022 and p = 0.0017, respectively). Furthermore, the circulating levels of miR-30b-5p were significantly lower in pregnant women when compared to young women (p <0.001). Supporting the findings from serum, the ovarian expression of miR-30b-5p increased during folliculogenesis with the highest expression in antral follicles.

Conclusion: In girls, circulating miR-30b-5p levels followed both the deactivation and reactivation of the HPG axis as observed during minipuberty and puberty, respectively. These findings support a regulatory role of miR-30b-5p on the HPG axis at the hypothalamic level in the onset of puberty in girls. We cannot deduce whether the dynamics of circulating levels of miR-30b-5p is a direct proxy of hypothalamic miR-30b-5p or also a product of ovarian activity.