scholarly journals The Effects of Kisspeptin-10 on Reproductive Hormone Release Show Sexual Dimorphism in Humans

2011 ◽  
Vol 96 (12) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Channa N. Jayasena ◽  
Gurjinder M. K. Nijher ◽  
Alexander N. Comninos ◽  
Ali Abbara ◽  
Adam Januszewki ◽  
...  

Abstract Background: Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspeptin is to be useful for treating reproductive disease, its effects in both men and women must be established. Aim: To compare the effects of kisspeptin-10 administration on reproductive hormone release in healthy men and women. Methods: Intravenous bolus kisspeptin-10 was administered to men and women (n = 4–5 per group). Subcutaneous bolus and iv infusion of kisspeptin-10 was also administered to female women (n = 4–5 per group). Circulating reproductive hormones were measured. Results: In healthy men, serum LH and FSH were elevated after iv bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively. In healthy women during the follicular phase of the menstrual cycle, no alterations in serum gonadotropins were observed after iv bolus, sc bolus, or iv infusion of kisspeptin-10 at maximal doses of 10 nmol/kg, 32 nmol/kg, and 720pmol/kg/min, respectively. In women during the preovulatory phase, serum LH and FSH were elevated after iv bolus kisspeptin-10 (10 nmol/kg). Conclusion: Kisspeptin-10 stimulates gonadotropin release in men as well as women during the preovulatory phase of menstrual cycle but fails to stimulate gonadotropin release in women during the follicular phase. The sexual dimorphism of the responsiveness of healthy men and women to kisspeptin-10 administration has important clinical implications for the potential of kisspeptin-10 to treat disorders of reproduction.

2013 ◽  
Vol 98 (11) ◽  
pp. 4464-4474 ◽  
Author(s):  
C. N. Jayasena ◽  
A. N. Comninos ◽  
G. M. K. Nijher ◽  
A. Abbara ◽  
A. De Silva ◽  
...  

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.


1997 ◽  
Vol 83 (2) ◽  
pp. 599-607 ◽  
Author(s):  
Dimitar Sajkov ◽  
Alister Neill ◽  
Nicholas A. Saunders ◽  
R. Douglas McEvoy

Sajkov, Dimitar, Alister Neill, Nicholas A. Saunders, and R. Douglas McEvoy. Comparison of the effects of sustained isocapnic hypoxia on ventilation in men and women. J. Appl. Physiol. 83(2): 599–607, 1997.—Sleep-related respiratory disturbances are more common in men than in premenopausal women. This might, in part, be due to different susceptibilities to the respiratory depressant effects of hypoxia. Therefore, we compared ventilation during 10 min of baseline room-air breathing and 20-min sustained isocapnic hypoxia (fractional inspired O2 = 11%, arterial saturation of O2 ≈ 80%) followed by 10 min of breathing 100% O2 in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O2 (10 min) and averaged. Inspired minute ventilation (V˙i) after 2 min of hypoxia was the same in men and women [131 ± 6.1% baseline for men, 136 ± 7.7% baseline for women; not significant (NS)] and declined to the same level after 20 min (115 ± 5.0% baseline for men, 116 ± 6.6% baseline for women; NS) associated with a similar decline in inspiratory time and tidal volume. Breathing frequency did not change.V˙i decreased transiently during subsequent 100% O2 breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall inV˙i was significantly greater than that observed during control hyperoxia experiments in men but not in women. We conclude that ventilatory responses to sustained isocapnic hypoxia do not differ between awake healthy men and women in the follicular phase of their menstrual cycle. However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.


2020 ◽  
Vol 105 (6) ◽  
pp. 1899-1905
Author(s):  
Chioma Izzi-Engbeaya ◽  
Sophie Jones ◽  
Yoshibye Crustna ◽  
Pratibha C Machenahalli ◽  
Deborah Papadopoulou ◽  
...  

Abstract Context Glucagon increases energy expenditure; consequently, glucagon receptor agonists are in development for the treatment of obesity. Obesity negatively affects the reproductive axis, and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects of glucagon receptor agonism on reproductive hormones is important for developing therapeutics for obesity; but reports in the literature about the effects of glucagon receptor agonism on the reproductive axis are conflicting. Objective The objective of this work is to investigate the effect of glucagon administration on reproductive hormone secretion in healthy young men. Design A single-blinded, randomized, placebo-controlled crossover study was conducted. Setting The setting of this study was the Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy eugonadal men (mean ± SEM: age 25.1 ± 1.0 years; body mass index 22.5 ± 0.4 kg/m2; testosterone 21.2 ± 1.2 nmol/L) participated in this study. Intervention An 8-hour intravenous infusion of 2 pmol/kg/min glucagon or rate-matched vehicle infusion was administered. Main Outcome Measures Luteinizing hormone (LH) pulsatility; LH, follicle-stimulating hormone (FSH), and testosterone levels were measured. Results Although glucagon administration induced metabolic effects (insulin area under the curve: vehicle 1065 ± 292 min.µU/mL vs glucagon 2098 ± 358 min.µU/mL, P < .001), it did not affect LH pulsatility (number of LH pulses/500 min: vehicle 4.7 ± 0.4, glucagon 4.2 ± 0.4, P = .22). Additionally, there were no significant differences in circulating LH, FSH, or testosterone levels during glucagon administration compared with vehicle administration. Conclusions Acute administration of a metabolically active dose of glucagon does not alter reproductive hormone secretion in healthy men. These data are important for the continued development of glucagon-based treatments for obesity.


1989 ◽  
Vol 121 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Janet A. Amico ◽  
Donald W. Richardson ◽  
Stephen J. Winters

Abstract. The effect of iv administration of synthetic oxytocin upon the pulsatile pattern of LH secretion was studied in 5 healthy men and 10 healthy women. Five of the women were studied in the follicular phase of a menstrual cycle and the other 5 were studied in the luteal phase of a cycle. Synthetic oxytocin in 0.9% saline or saline alone was administered via continuous iv infusion for 8 h on 2 consecutive days. Infusions were administered using a double-blinded and radomized schedule. The rate of the oxytocin infusion commenced at 1 mU/min and was increased 1 mU/min every 40 min to a final rate of 12 mU/min. The plasma oxytocin concentration during oxytocin infusion ranged from 2–70 fmol/l. Blood for LH determination was sampled every 20 min in the 5 follicular phase women and every 10 min in the 5 men and 5 luteal phase women. The detect algorithm was used to analyze LH pulsatile secretion. Oxytocin infusion was without significant effect on mean LH, number of LH pulses, or area under the LH curve in men or women studied for the period of observation. Thus it is unlikely that increases in plasma oxytocin regulate the pulsatile secretion of LH in humans.


1998 ◽  
Vol 83 (6) ◽  
pp. 2099-2103 ◽  
Author(s):  
A. R. Genazzani ◽  
F. Petraglia ◽  
F. Bernardi ◽  
E. Casarosa ◽  
C. Salvestroni ◽  
...  

Allopregnanolone is a neuroactive steroid involved in modulating behavioral functions, stress, and neuroendocrine axes in rats. Changes in plasma allopregnanolone levels throughout the menstrual cycle have been reported in healthy women, but there exists no information on the possible gender or age-related changes or on the source(s) of circulating allopregnanolone. The aim of the present study was to assess serum allopregnanolone concentrations according to gender, menstrual cycle, age, and menopause in normal men and women; serum progesterone (P) and dehydroepiandrosterone (DHEA) levels were evaluated in the same specimens. In addition, the possible source of circulating allopregnanolone in fertile women was investigated by using stimulatory and inhibitory endocrine tests acting on the ovary and/or adrenal cortex. The present study included 189 fertile women, 112 postmenopausal women, and 46 men. Serum steroid levels were determined after extraction, using specific RIAs. Allopregnanolone levels in fertile women in the follicular phase were similar to those in age-matched men; no significant difference was found between fertile women in the follicular phase and postmenopausal women. The highest levels were found in fertile women during the luteal phase (P< 0.01). An age-related decrease was observed in men (P < 0.01), but not in women. P and DHEA levels were significantly higher in women than in men and were higher in fertile women than in postmenopausal women (P < 0.01). Both P and DHEA showed an age-related decrease in men and women (P < 0.01). Serum allopregnanolone and P, but not DHEA, significantly increased in response to a GnRH test, whereas corticotropin-releasing factor and ACTH tests elicited a significant increase in allopregnanolone, P, and DHEA levels (P < 0.01). The suppression of adrenal steroidogenesis by dexamethasone markedly reduced both allopregnanolone and DHEA serum levels (P < 0.01). In conclusion, the present study demonstrated that although men show an age-related decrease, serum allopregnanolone levels in women do not change with age and correlate with P levels during the menstrual cycle and in response to endocrine tests. Ovary and adrenal cortex may be major sources of circulating allopregnanolone in fertile women.


1986 ◽  
Vol 110 (1) ◽  
pp. 19-26 ◽  
Author(s):  
S. L. Alexander ◽  
C. H. G. Irvine

ABSTRACT Luteinizing hormone release induced by a range of small (3·3–33 μg) and large (300–500 μg) i.v. doses of gonadotrophin-releasing hormone (GnRH) was measured in acyclic (n = 4), luteal phase (n = 3) and follicular phase (n = 5) mares and compared with endogenously generated LH pulses in the same reproductive states. Extrapolation from log–linear dose–response curves showed that an LH pulse comparable to an endogenous one would be simulated by i.v. injection of 7·0 (n = 4) and 4·1 (n = 6) μg GnRH in luteal and follicular phase mares respectively; a much smaller dose than the 500 μg usually given clinically or experimentally. In acyclic mares (n = 4), LH pulses occurred too infrequently to be characterized. At small doses of GnRH the amount of LH released by the same dose was similar in all three reproductive states, although the steroid hormone milieu differed markedly. This implies that observed differences between states in mean (± s.e.m.) serum LH concentrations (0·7 ± 0·01, 1·2 ± 0·03 and 11·6 ± 0·33 (μg/l) in acyclic, luteal and follicular phase mares respectively) were produced by differences in GnRH pulse frequency and/or amplitude and not by steroid-mediated changes in pituitary response to GnRH. In acyclic, luteal and follicular phase mares, LH pulse frequency was: immeasurably low, 0·09 and 1·14 pulses/h respectively, which supports the important contribution of pulse frequency to determining mean LH concentration. The LH response to large doses of GnRH was significantly greater in the luteal than in the follicular phase, and was greater than the response to 33 μg in the luteal phase but not in the other two states. Thus, to a large but not to a small dose of GnRH, the pituitary appeared most responsive in the luteal phase. Therefore, in studies of the physiology of the hypothalamic-pituitary system, small doses of GnRH, which induce physiologically sized LH responses, may be preferred to large doses, which result in a level of stimulation to which the pituitary is never naturally exposed and to which it may respond in a non-physiological manner. J. Endocr. (1986) 110, 19–26


2021 ◽  
Vol 6 (1) ◽  
pp. 327-331
Author(s):  
L. D. Popova ◽  
I. M. Vasylyeva ◽  
O. A. Nakonechna

The excessive aggression is an actual problem of modern society but the mechanisms of aggressiveness development have not been sufficiently investigated. Women aggression is considered to differ from men one and results obtained on males cannot be extrapolated on females. Sex hormones have a crucial role in the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood. Hypothalamic pituitary adrenal axis and sympathoadrenal system are major neuroendocrine systems that respond to stress. Stress hormones are involved into behavioral reactions of organism. Gonadal, hypothalamic pituitary adrenal axes, and sympathoadrenal system are tightly interrelated and every of them can influence another one. The purpose of the study was to estimate correlation differences between sex and stress hormones in men and women. Material and methods. Forty healthy young people aged 18 to 22 years with a body mass index of 19-24 (21 women and 19 men) were enrolled in the study. Hormone levels in blood serum were determined by Testosterone, Estradiol, Cortisol ELISA kits (Italy), Epinephrine/Norepinephrine (EPI) ELISA kit (China). Results and discussion. In all phases of the menstrual cycle, the level of cortisol in women was lower than in men, but in the luteal phase these differences were not statistically significant. In all phases of the menstrual cycle, the blood serum norepinephrine content in women was lower than in men, but in the follicular phase these differences were not statistically significant. The level of epinephrine in women during ovulation and luteal phase did not differ from the level of epinephrine in men, but in follicular phase it was significantly lower. Calculations of correlations between individual hormones revealed a significant difference between them in men and women. Positive correlations between testosterone and estradiol and between cortisol and epinephrine; a strong negative correlation between epinephrine and testosterone/norepinephrine ratio were found in men. Positive correlation between testosterone and cortisol and negative correlation between estradiol and cortisol/testosterone ratio were revealed in women. Conclusion. In women, strong correlations were found between cortisol and sex hormones; in men, strong interrelationship was revealed between cortisol and epinephrine. Both in men and in women (in all phases of the menstrual cycle), high positive correlations between testosterone/norepinephrine and cortisol/norepinephrine ratios were observed


2021 ◽  
Vol 11 (1) ◽  
pp. 156-160
Author(s):  
Dhamia Ahmed Attia ◽  
Najdat Ali Al-kadhi ◽  
Iktefa Abdul Hamid Mohammed Saeed ◽  
Kasim Sakran Abass

2005 ◽  
Vol 98 (3) ◽  
pp. 822-828 ◽  
Author(s):  
Dennis Jensen ◽  
Larry A. Wolfe ◽  
Denis E. O'Donnell ◽  
Gregory A. L. Davies

This study used a modified CO2 rebreathing procedure to examine the effect of gender on the chemoreflex control of breathing during wakefulness in healthy men ( n = 14) and women ( n = 14). Women were tested in the follicular phase of the menstrual cycle. During rebreathing trials, subjects hyperventilated to reduce the partial pressure of end-tidal CO2 (PetCO2) below 25 Torr and were then switched to a rebreathing bag containing a normocapnic hypoxic or hyperoxic gas mixture. During the trial, PetCO2 increased, while O2 was maintained at a constant level. The point at which ventilation began to rise as PetCO2 increased was identified as the ventilatory recruitment threshold (VRT). Ventilation below the VRT was measured, and the slope of the ventilatory response above the VRT was determined. Gender had no effect on the hyperoxic or hypoxic VRT for CO2. Central chemoreflex sensitivity was significantly greater in men than women but not after correction for forced vital capacity. Measures of peripheral chemoreflex sensitivity were similar between genders. However, the slope of the tidal volume (Vt) response to hyperoxic and hypoxic CO2 rebreathing (corrected and uncorrected) was greater in men than women, respectively. We conclude that central chemoreflex sensitivity is greater in men compared with women as reflected by differences in ventilatory (uncorrected) and Vt (corrected and uncorrected) responses to CO2. However, gender has no significant effect on the central chemoreflex VRT for CO2. The peripheral chemoreflex control of breathing during wakefulness is similar between men and women.


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