Circulating MKRN3 Levels Decline Prior to Pubertal Onset and Through Puberty: A Longitudinal Study of Healthy Girls

Abstract

Declining levels of circulating MKRN3 preceded pubertal onset. The negative correlation between MKRN3 and gonadotropins further supports MKRN3 as a major regulator of hypothalamic GnRH secretion during childhood. Undetectable or low MKRN3 levels were observed in a subgroup of patients with early onset of puberty.

Circulating makorin ring finger protein 3 levels decline in boys before the clinical onset of puberty

“…These findings are in agreement with the results of the recent study in girls (5). In boys, however, the change in MKRN3 levels appears biphasic with a rapid decline prior to clinical onset of puberty and slower changes thereafter once puberty progresses, whereas in girls, the decline in serum MKRN3 continued to mid-puberty (5).…”

“…There are currently two publications on circulating MKRN3 levels in humans (5,6,7). In girls, MKRN3 levels declined before the onset of puberty and correlated negatively with increasing gonadotropin levels (5), which further underpins the potential role of MKRN3 in the central inhibitory control of puberty. In adult men, circulating MKRN3 levels did not seem to reflect the integrity of the hypothalamic-pituitary-gonadal (HPG) axis (6,7), as the levels were similar in men with hypogonadal or normal testosterone levels.…”

“…In humans, MKRN3 is expressed not only in the hypothalamus (3) but also in other tissues (4). There are currently two publications on circulating MKRN3 levels in humans (5,6,7). In girls, MKRN3 levels declined before the onset of puberty and correlated negatively with increasing gonadotropin levels (5), which further underpins the potential role of MKRN3 in the central inhibitory control of puberty.…”

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

“…A recent genome wide-association study identified two single-nucleotide polymorphisms of MKRN3 significantly associated with an older age at menarche only when inherited from the father (19). These SNPs were not associated with serum MKRN3 concentration (18), but they might be associated with a persistence of intracellular MKRN3 activity for a longer period of time after birth than for the WT allele (18).…”

“…It has been suggested that the MKRN3 protein inhibits GnRH secretion in mice (11). A recent study on a large group of healthy Danish girls showed that serum MKRN3 concentration declined before the onset of puberty and was lower in a subset of girls with early puberty onset than in the subset of age-matched prepubertal girls (18). A recent genome wide-association study identified two single-nucleotide polymorphisms of MKRN3 significantly associated with an older age at menarche only when inherited from the father (19).…”