Endogenous opioids and hypogonadism in human obesity
Related Experiment Videos
D M Blank1, R V Clark, S B Heymsfield
1Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322.
Abstract:
Massively obese males often show symptoms of hypogonadism, but the mechanism for this is unclear. Increased endogenous opioid inhibition of the hypothalamic GnRH pulse generator resulting in insufficient stimulation of the pituitary gonadotroph has been proposed as a possible mechanism. If this hypothesis is correct, obese males should be more sensitive to the LH-elevating effects of the opiate antagonist, naloxone, than men of normal weight and gonadal status. This study investigated the etiology of obesity-related hypogonadism by examining luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) and to infusions of saline or naloxone. Subjects were five obese (201 +/- 14% IBW) and five normal weight (control) (97 +/- 4% IBW) males. Before treatment, obese males had significantly (p < 0.05) lower testosterone levels than control subjects (307 +/- 72 vs. 597 +/- 49 ng/dl), whereas estradiol, androstenedione, and dehydroepiandrosterone levels were not different between the two groups. Both groups showed equivalent elevations in LH (fourfold to sixfold) in response to GnRH stimulation, but obese patients had significantly lower basal (p < 0.05) and GnRH-stimulated (p < 0.01) FSH levels. Infusions of naloxone (but not saline) led to significant (p < 0.01) increases in LH above preinfusion baseline levels (20.5 +/- 2.8% in obese and 28.6 +/- 6.3% in controls). In control subjects, integrated LH levels during naloxone infusion were not significantly elevated above those found during saline infusion, while obese subjects exhibited a 43% augmentation of integrated LH (31.0 +/- 5.3 ng/ml during naloxone vs. 21.7 +/- 1.8 ng/ml during saline, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Obese males with hypogonadism show increased luteinizing hormone (LH) response to naloxone, suggesting opioid pathways contribute to this condition. This indicates obesity-related hypogonadism may be reversed with opiate antagonists.
Area of Science:
- Endocrinology
- Reproductive Medicine
- Obesity Research
Background:
- Massively obese males frequently exhibit hypogonadism, a condition with an unclear underlying mechanism.
- A proposed mechanism involves increased endogenous opioid inhibition of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, leading to insufficient pituitary gonadotroph stimulation.
Purpose of the Study:
- To investigate the etiology of obesity-related hypogonadism.
- To examine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to GnRH and naloxone infusions in obese and normal-weight males.
Main Methods:
- Five massively obese males (201% IBW) and five normal-weight males (97% IBW) were studied.
- Hormonal levels (testosterone, estradiol, androstenedione, dehydroepiandrosterone) were measured.
- Responses to GnRH stimulation and infusions of saline or naloxone were assessed by measuring LH and FSH levels.
Main Results:
- Obese males had significantly lower basal testosterone levels compared to controls.
- Both groups showed similar LH elevations after GnRH, but obese males had lower basal and GnRH-stimulated FSH levels.
- Naloxone infusion significantly increased LH levels in both groups, with obese subjects showing a greater augmentation of integrated LH compared to saline infusion.
Conclusions:
- Obese males exhibit altered gonadotropin responses and are more sensitive to the LH-elevating effects of naloxone, supporting the hypothesis of increased opioid inhibition.
- These findings suggest that obesity-related hypogonadism may be partly mediated by endogenous opioid pathways.
- Naloxone's efficacy in increasing LH in obese males indicates a potential therapeutic target for managing hypogonadism in obesity.