Intranasal Kisspeptin Administration Stimulates Reproductive Hormone Secretion in Healthy Men

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.

Download Full-text

Regulation of reproductive hormone secretion in primates by short-term changes in nutrition

Reviews of Reproduction ◽

10.1530/ror.0.0010117 ◽

1996 ◽

Vol 1 (2) ◽

pp. 117-126 ◽

Cited By ~ 67

Author(s):

J. Cameron

Keyword(s):

Hormone Secretion ◽

Reproductive Hormone ◽

Short Term

Download Full-text

Changes in urinary testosterone and corticosterone metabolites during short-term confinement with repeated handling in wild male cane toads (Rhinella marina)

Australian Journal of Zoology ◽

10.1071/zo11070 ◽

2011 ◽

Vol 59 (4) ◽

pp. 264 ◽

Cited By ~ 14

Author(s):

Edward J. Narayan ◽

Frank C. Molinia ◽

John F. Cockrem ◽

Jean-Marc Hero

Keyword(s):

Adult Male ◽

Reproductive Effort ◽

Hormone Secretion ◽

Reproductive Hormone ◽

Cane Toad ◽

Short Term ◽

Rhinella Marina ◽

Testosterone Secretion ◽

Metabolite Concentrations ◽

Corticosterone Metabolites

Stressors generally decrease testosterone secretion and inhibit reproduction in animals. Urinary testosterone and corticosterone metabolite concentrations were measured in adult male cane toads (Rhinella marina) at the time of capture from the wild and during 24 h of confinement with repeated handling. Mean urinary testosterone concentrations increased 2 h after capture, were significantly elevated above initial concentrations at 5 h, and then declined. Mean testosterone concentrations remained elevated 24 h after capture. Mean urinary corticosterone concentrations increased after capture, were significantly elevated above initial concentrations at 2 h, and remained elevated thereafter. This is the first report in amphibians of an increase in testosterone excretion after capture from the wild, with previous studies showing either no change or decline in testosterone. This finding may be associated with the mating strategy and maintenance of reproductive effort in the cane toad, a species that shows explosive breeding and agonistic male–male interactions during breeding. The finding that testosterone excretion increases rather than decreases after capture in male cane toads shows that it should not be generally assumed that reproductive hormone secretion will decrease after capture in amphibians.

Download Full-text

Interleukin-2 Transiently Inhibits Pulsatile Growth Hormone Secretion in Young but not Older Healthy Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab484 ◽

2021 ◽

Author(s):

Ferdinand Roelfsema ◽

Rebecca Yang ◽

Johannes D Veldhuis

Keyword(s):

Hormone Secretion ◽

Interleukin 2 ◽

Age Groups ◽

Growth Hormone Secretion ◽

Experimental Conditions ◽

Deconvolution Analysis ◽

Healthy Men ◽

Gh Secretion ◽

Older Subjects ◽

Young Subjects

Abstract Context Interleukin-2 (IL2), a proinflammatory cytokine, has been used to treat malignancies. Increased cortisol and ACTH were noted, but GH secretion was not investigated in detail. Objective We quantified GH secretion after a single sc injection of IL2 in 17 young and 18 older healthy men in relation to dose, age and body composition. Design This was a placebo-controlled, blinded, prospectively randomized cross-over study. At 20:00 h IL2 (3 or 6 million units per m2 ) or saline was injected sc. Lights were off between 23:00 and 07:00 h. Blood was sampled at 10-min intervals for 24 h. Outcome measures Deconvolution analysis of GH secretion. Results GH profiles were pulsatile under both experimental conditions and lower in older than young volunteers. Since the effect of IL2 might be time-limited, GH analyses were performed on the complete 24-h series and the 6 h after IL2 administration. Total and pulsatile 24-h GH secretion decreased nonsignificantly. Pulsatile secretion fell over the first 6 h after IL2 (P=0.034), with visceral fat as covariate (P=0.003), but not age(P=0.10). Plots of cumulative 2-h bins of GH pulse mass showed a distinction by treatment and age groups: a temporary GH decrease of 32% and 28% occurred in the first 2-h bins after midnight (P=0.019 and 0.038) in young subjects, while in older subjects no differences were present at any time point. Conclusion This study demonstrates that IL2 temporarily diminishes GH secretion in young, but not elderly, men.

Download Full-text

Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Animals ◽

10.3390/ani10020313 ◽

2020 ◽

Vol 10 (2) ◽

pp. 313 ◽

Cited By ~ 2

Author(s):

Rihong Guo ◽

Fang Chen ◽

Cheng Mei ◽

Zicun Dai ◽

Leyan Yan ◽

...

Keyword(s):

Dairy Cows ◽

Reproductive Performance ◽

Luteal Phase ◽

Low Dose ◽

Follicle Stimulating Hormone ◽

Hormone Secretion ◽

Plasma Concentrations ◽

High Dose ◽

Reproductive Hormone ◽

Conception Rates

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

Download Full-text

Incretin and islet hormonal responses to fat and protein ingestion in healthy men

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90233.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. E779-E784 ◽

Cited By ~ 109

Author(s):

Richard D. Carr ◽

Marianne O. Larsen ◽

Maria Sörhede Winzell ◽

Katarina Jelic ◽

Ola Lindgren ◽

...

Keyword(s):

Hormone Secretion ◽

Plain Water ◽

Islet Function ◽

Carbohydrate Ingestion ◽

Healthy Men ◽

Dipeptidyl Peptidase 4 ◽

Water Ingestion ◽

Islet Hormones ◽

Protein Ingestion ◽

Islet Hormone

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of noncarbohydrate macronutrients is not known. This study therefore examined integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20–25 yr ( n = 12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1, and GIP levels and DPP-4 activity were stable during the 5-h study period. Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion ( P < 0.001). This was associated with sevenfold higher insulin and glucagon responses compared with fat ingestion (both P < 0.001). After protein, the early GIP, but not GLP-1, responses correlated to insulin ( r2= 0.86; P = 0.0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that, whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion.

Download Full-text

Peak Bone Mass in Young Healthy Men Is Correlated with the Magnitude of Endogenous Growth Hormone Secretion

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.83.10.3463 ◽

1998 ◽

Vol 83 (10) ◽

pp. 3463-3468 ◽

Cited By ~ 6

Author(s):

M. Russell-Aulet

Keyword(s):

Growth Hormone ◽

Bone Mass ◽

Endogenous Growth ◽

Peak Bone Mass ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Healthy Men

Download Full-text

Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00222.2015 ◽

2016 ◽

Vol 310 (1) ◽

pp. G43-G51 ◽

Cited By ~ 27

Author(s):

Simon Veedfald ◽

Astrid Plamboeck ◽

Carolyn F. Deacon ◽

Bolette Hartmann ◽

Filip K. Knop ◽

...

Keyword(s):

Hormone Secretion ◽

Sham Feeding ◽

C Peptide ◽

Healthy Men ◽

Glucose Levels ◽

Gut Hormone ◽

Cephalic Phase ◽

Hormone Responses ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

Download Full-text