The role of kisspeptin and MKRN3 in the diagnosis of central precocious puberty in girls

Abstract

Objective: To evaluate the characteristics and significance of serum kisspeptin and MKRN3 levels for the diagnostic of central precocious puberty (CPP) in girls. Method: 34 individuals with CPP, 17 individuals with premature thelarche (PT) and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included of body mass index and tests for breast, bone and sexual characteristics were carried out. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3 and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90 and 120min after injection with triptorelin. Results: Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P=0.020), while serum MKRN3 levels lower in the two groups (P=0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P<0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40nmol/L, with 82.4% sensitivity and 57.1% specificity; while the cut-off value of serum MKRN3 was 0.33pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5. Conclusions: Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.

The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction

“…They found the median serum kisspeptin levels were significantly higher in IUP women (1.50ng/ml) than in SAB women (0.20ng/ml), indicating that kisspeptin is detectable in serum in early pregnancy and can discriminate SAB from IUP (168). Also, as mentioned above, girls with CPP had higher serum kisspeptin levels compared with healthy girls (109)(110)(111). However, serum kisspeptin levels are not able to become a single diagnostic tool because the evident overlap limits its use, while it may still be useful as an adjunctive tool in the diagnosis of CPP.…”

“…In 2008, a mutation (Arg386Pro) in the kisspeptin receptor gene which results in extended activation of intracellular signaling pathways when responding to kisspeptin was identified in a girl with idiopathic CPP (108). Many studies have confirmed that girls with CPP had higher serum kisspeptin levels than normal controls (109)(110)(111). It suggested that the mutant may increase the promoting effects of kisspeptin on GnRH release, thereby speeding up the HPG axis maturation.…”

Hormone supply to the pituitary gland: A comprehensive investigation of female‑related tumors (Review)

“…These are also critical regulators of steroid generation, cell proliferation and migration, and cytoskeleton remodeling (100). Concurrently, makorin ring-finger protein 3 (MKRN3) inhibits the reproductive axis through its role in kisspeptin-expressing neurons involved in a MKRN3-guided ubiquitination mediation mechanism (101,102). A previous study revealed that a high-fat diet (HFD) intake by parents may also be a risk factor for prostate hyperplasia and cancer at advanced ages, due to a negative impact on the reproductive system of male offspring (102,103).…”

“…Concurrently, makorin ring-finger protein 3 (MKRN3) inhibits the reproductive axis through its role in kisspeptin-expressing neurons involved in a MKRN3-guided ubiquitination mediation mechanism (101,102). A previous study revealed that a high-fat diet (HFD) intake by parents may also be a risk factor for prostate hyperplasia and cancer at advanced ages, due to a negative impact on the reproductive system of male offspring (102,103). Thus, it is advised that epidemiological and clinical research on semen quality must include male offspring of overweight and/or obese parents (103,104).…”

Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction

“…Central precocious puberty (CPP) is caused by the early reactivation of the HPO axis, with the development of secondary sexual characteristics before the age of 8 in girls and 9 in boys [ 140 , 141 ]. In addition, several studies have shown that the level of serum kisspeptin increased significantly in CPP patients [ 142 – 146 ], suggesting serum kisspeptin level can be used as a potential biomarker in diagnosing CPP.…”