Abstract

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

Highlights

  • Kisspeptin is a hormone that promotes the onset of puberty by stimulating the secretion of gonadotropin-stimulating hormone (GnRH)

  • We found that plasma kisspeptin levels in Prader–Willi Syndrome (PWS) patients with growth hormone (GH) deficiency were similar to those in obese subjects matched by age, sex, and body mass index (BMI) and were higher than those in healthy controls

  • After 12 months of treatment with GH, plasma kisspeptin levels in PWS patients decreased to levels similar to those observed in healthy subjects

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Summary

Introduction

Kisspeptin is a hormone that promotes the onset of puberty by stimulating the secretion of gonadotropin-stimulating hormone (GnRH). Kisspeptin can stimulate the release of other pituitary hormones such as prolactin, growth hormone (GH), oxytocin, and vasopressin [1]. Kisspeptin is mainly synthesized by neurons in the arcuate nucleus of the hypothalamus. Its synthesis is modulated by energy balance, decreasing in situations of insufficient weight (e.g., anorexia nervosa) or excess weight (e.g., obesity) [2]. Low kisspeptin levels are considered the cause of the hypogonadotropic hypogonadism seen in some patients with metabolic syndrome and obesity [2,3]. Kisspeptin-producing neurons express receptors for leptin, a hormone produced in adipose tissue that informs these neurons about the status of energy reserves [4,5]

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