Abstract
PurposeTo evaluate the temporal coupling between spontaneous kisspeptin and luteinizing hormone (LH) pulsatile releases in polycystic ovary syndrome (PCOS) patients.MethodsWe examined 71 patients diagnosed with PCOS. A 2 h pulsatility study was performed to evaluate serum kisspeptin and LH pulse frequency and concentration, sampled every 10 min; baseline follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), cortisol, 17-hydroksy-progesterone (17OHP), testosterone (T), free testosterone index (FTI, and insulin levels were also measured. Detect and Specific Concordance (SC) algorithms were used to evaluate the temporal coupling associations between spontaneous episodic secretion of kisspeptin and LH.ResultsAll PCOS patients demonstrated LH and kisspeptin pulsatile secretions. When the SC index was calculated across the sample of PCOS patients (n = 71), no temporal coupling was observed between kisspeptin and LH pulses. When PCOS patients were subdivided according to their menstrual cyclicity, oligomenorrheic patients demonstrated elevated kisspeptin pulse frequency. Additionally, the SC index reveled a temporal coupling between kisspeptin and LH secretory peaks only in eumenorrheic patients (n = 30, intermenstrual interval < 45 days). Oligomenorrheic PCOS patients (intermenstrual interval > 45 days) did not demonstrate temporal coupling between kisspeptin and LH secretory peaks.ConclusionsThe study of the endogenous kisspeptin and LH pulsatile release revealed the temporal coupling of kisspeptin with LH secretory pulses only in eumenorrheic. This data supports the hypothesis that neuroendocrine impairments in PCOS affect the coupling of kisspeptin with LH pulses and potentially worsen as the disease progresses, becoming unequivocally evident in oligomenorrheic PCOS patients.
Highlights
Identifying kisspeptin as a key mediator of gonadotropinreleasing hormone (GnRH) secretion has led to a new understanding of neuroendocrine regulation in humanElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Kisspeptin plays a principal role in the regulation of gonadotropin secretion, the onset of puberty, sex hormonemediated feedback, and adult fertility
The aim of this study is to investigate the association between spontaneous episodic secretion of kisspeptin and its temporal coupling with luteinizing hormone (LH) secretory pulses in a large sample size of PCOS patients
When analyzing the time series of kisspeptin and LH, the Detect algorithm demonstrated the presence of spontaneous episodic events of LH and kisspeptin, both with a distinct pulsatile release pattern during the 2 h pulsatility study (Table 2)
Summary
Identifying kisspeptin as a key mediator of gonadotropinreleasing hormone (GnRH) secretion has led to a new understanding of neuroendocrine regulation in human. Kisspeptin plays a principal role in the regulation of gonadotropin secretion, the onset of puberty, sex hormonemediated feedback, and adult fertility. Dose, and route of administration, kisspeptin has been shown to enhance secretion and pulse frequency of luteinizing hormone (LH) [1, 2]. Following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), kisspeptin directly stimulates GnRH neurons to induce and modulate pulsatile GnRH release [3]. Human kisspeptin neurons are located primarily in two areas: the preoptic area and the hypothalamic arcuate nucleus (ARC), known as the infundibular nucleus
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