scholarly journals Kisspeptin and neurokinin B interactions in modulating gonadotropin secretion in women with polycystic ovary syndrome

2020 ◽  
Vol 35 (6) ◽  
pp. 1421-1431
Author(s):  
Karolina Skorupskaite ◽  
Jyothis T George ◽  
Johannes D Veldhuis ◽  
Robert P Millar ◽  
Richard A Anderson
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Clinical Research ◽  
Polycystic Ovary ◽  
Pulse Frequency ◽  
Research Facility ◽  
Neurokinin B ◽  
Ovary Syndrome ◽  
Clinical Research Facility ◽  
Lh Secretion

Abstract STUDY QUESTION What is the role of the hypothalamic neuropeptide neurokinin B (NKB) and its interaction with kisspeptin on GnRH/LH secretion in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Administration of neurokinin 3 receptor antagonist (NK3Ra) for 7 days reduced LH and FSH secretion and LH pulse frequency in women with PCOS, whilst the stimulatory LH response to kisspeptin-10 was maintained. WHAT IS KNOWN ALREADY PCOS is characterized by abnormal GnRH/LH secretion. NKB and kisspeptin are master regulators of GnRH/LH secretion, but their role in PCOS is unclear. STUDY DESIGN, SIZE, DURATION The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7). On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion. This was repeated with the alternate infusion in a subsequent cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects were women with PCOS, studied in a Clinical Research Facility. Reproductive hormones were measured before and after NK3Ra administration. On the last day of NK3Ra administration (or the equivalent cycle day in untreated women), all women attended for an 8-h frequent blood sampling to allow analysis of the pulsatile LH secretion. MAIN RESULTS AND THE ROLE OF CHANCE NK3Ra reduced LH secretion (4.0 ± 0.4 vs 6.5 ± 0.8 IU/l, P < 0.05) and pulse frequency (0.5 ± 0.1 vs 0.8 ± 0.1 pulses/h, P < 0.05); FSH secretion was also reduced (2.0 ± 0.3 vs 2.5 ± 0.4 IU/l, P < 0.05). Without NK3Ra pre-treatment, kisspeptin-10 increased LH secretion (5.2 ± 0.5 to 7.8 ± 1.0 IU/L, P < 0.05), with a positive relationship to oestradiol concentrations (r2 = 0.59, P < 0.05). After NK3Ra administration, the LH response to kisspeptin-10 was preserved (vehicle 3.5 ± 0.3 vs 9.0 ± 2.2 IU/l with kisspeptin-10, P < 0.05), but the positive correlation with oestradiol concentrations was abolished (r2 = 0.07, ns. after NK3Ra). FSH secretion was increased by kisspeptin-10 after NK3Ra treatment, but not without NK3Ra treatment. LIMITATIONS, REASONS FOR CAUTION The study did not explore the dose relationship of the effect of NK3R antagonism. The impact of obesity or other aspects of the variability of the PCOS phenotype was not studied due to the small number of subjects. WIDER IMPLICATIONS OF THE FINDINGS These data demonstrate the interactive regulation of GnRH/LH secretion by NKB and kisspeptin in PCOS, and that the NKB system mediates aspects of oestrogenic feedback. STUDY FUNDING/COMPETING INTEREST(S) Wellcome Trust through Scottish Translational Medicine and Therapeutics Initiative (102419/Z/13/A) and MRC grants (G0701682 to R.P.M. and R.A.A.) and MR/N022556/1 to the MRC Centre for Reproductive Health. This work was performed within the Edinburgh Clinical Research Facility. J.T.G. has undertaken consultancy work for AstraZeneca and Takeda Pharmaceuticals and is an employee of Boehringer Ingelheim. R.P.M. has consulted for Ogeda and was CEO of Peptocrine. R.A.A. has undertaken consultancy work for Merck, Ferring, NeRRe Therapeutics and Sojournix Inc. J.D.V. and K.S. have nothing to disclose. TRIAL REGISTRATION NUMBER N/A.

Role of Prolactin in the Polycystic Ovary Syndrome

1980 ◽  
Vol 25 (4) ◽  
pp. S89-S93 ◽  
Author(s):  
Emilio del Pozo ◽  
Paolo Falaschi
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Control Mechanisms ◽  
Plasma Prolactin ◽  
Adrenal Androgen ◽  
Ovary Syndrome ◽  
Steroid Synthesis ◽  
Androgen Synthesis ◽  
Lh Secretion

Studies with a dopamine agonist (Bromocriptine) and an antagonist (Haloperidol) suggest that elevated sex steroid synthesis such as may be found in the polycystic ovary syndrome (PCO) influence the pituitary lactotrope response to endogenous control mechanisms. A distinction between PCO with occasional elevation of plasma prolactin (PRL) and the galactorrhoea-amenorrhoea syndrome (GA) associated with hyperprolactinaemia can be established on the basis of differences in circulating levels of sex steroids and in the pattern of response to lactotrope cell stimulation. Thus, adrenal androgen synthesis can be strengthened in GA whereas in PCO both pathways, adrenal and ovarian, may be overstimulated. Also blunted PRL response to TRH or dopaminergic blockade is often seen in GA. The use of bromocriptine in patients with PCO and elevated PRL plasma levels has been shown to restore ovulation. The possible implications of dopaminergic mechanisms in the control of LH secretion independent of PRL release are discussed.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review

2020 ◽  
pp. 1-8
Author(s):  
Daniela Menichini ◽  
Gianpiero Forte ◽  
Beatrice Orrù ◽  
Giuseppe Gullo ◽  
Vittorio Unfer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Polycystic Ovary Syndrome ◽  
Embryo Quality ◽  
Polycystic Ovary ◽  
Vitamin D Supplementation ◽  
Endometrial Receptivity ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
Beneficial Role

Abstract. Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400–800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

scholarly journals The role of serum β-trophin and endostatin in patients with polycystic ovary syndrome: Are they correlated?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Gong ◽  
Aikmu Bilixzi ◽  
Xinmei Wang ◽  
Yanli Lu ◽  
Li Wan ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Influencing Factors ◽  
Polycystic Ovary ◽  
Pearson Correlation ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Ovary Syndrome ◽  
Factors Affecting ◽  
Main Factors

Abstract Background It’s necessary to investigate the serum β-trophin and endostatin (ES) level and its influencing factors in patients with newly diagnosed polycystic ovary syndrome (PCOS). Methods Newly diagnosed PCOS patients treated in our hospital were selected, and healthy women who took physical examination during the same period as healthy controls. We detected and compared the related serum indicators between two groups, Pearson correlation were conducted to identify the factors associated with β-trophin and ES, and the influencing factors of β-trophin and ES were analyzed by logistic regression. Results A total of 62 PCOS patients and 65 healthy controls were included. The BMI, WHI, LH, FSH, TT, FAI, FBG, FINS, HOMA-IR, TC, TG, LDL, ES in PCOS patients were significantly higher than that of healthy controls, while the SHBG and HDL in PCOS patients were significantly lower than that of healthy controls (all p < 0.05). β-trophin was closely associated with BMI (r = 0.427), WHR (r = 0.504), FBG (r = 0.385), TG (r = 0.405) and LDL (r = 0.302, all p < 0.05), and ES was closely associated with BMI (r = 0.358), WHR (r = 0.421), FBG (r = 0.343), TC (r = 0.319), TG (r = 0.404, all p < 0.05). TG, BMI, WHR and FBG were the main factors affecting the serum β-trophin levels (all p < 0.05). FBG, TC and BMI were the main factors affecting the serum ES levels (all p < 0.05). The TG, β-trophin, ES level in PCOS patients with insulin resistance (IR) were significantly higher than that of those without IR (all p < 0.05). Conclusion Increased β-trophin is closely associated with increased ES in patients with PCOS, which may be the useful indicators for the management of PCOS.

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