Older men exhibit reduced efficacy of and heightened potency downregulation by intravenous pulses of recombinant human LH: a study in 92 healthy men
Open accessAbstract
Direct sampling of the human spermatic veins has disclosed concomitant LH and testosterone (T) pulses, suggesting pulsatile LH concentration-dependent stimulation of T secretion. However, studies to date have examined this hypothesis using only pharmacological stimulation with hCG. The present study tests the hypothesis that age is marked by decreased T secretory responses to repeated near-physiological iv pulses of recombinant human LH administered in a Clinical Translational Science Center. Participants included 92 healthy men aged 18–75 yr with BMI 18–34 kg/m 2. The contribution of endogenous LH pulses was minimized by combined injection of a selective GnRH receptor antagonist sc and successive pulses of biosynthetic LH iv. A new analytical dose response model was applied to estimate the properties of exogenous LH's drive of T secretion. Regression of LH-T dose response potency estimates on age showed that the efficacy of pulses of biosynthetic LH progressively decreased with age ( P = 0.014, r = 0.26). Testis sensitivity to exogenous LH pulses also declined with age ( P = 0.011, r = 0.27). Moreover, estimated Leydig cell downregulation by LH pulses rose significantly with age ( P = 0.039, r = 0.22). These outcomes were selective, since the recovery potency of infused LH was not affected by age but was reduced by increasing BMI ( P = 0.011, r = 0.27). Assuming stable bioactivity of infused recombinant human LH, these novel data indicate that factors associated with age and BMI attenuate LH efficacy and testis sensitivity and augment Leydig cell downregulation in healthy men.
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The reduction in LH and testosterone secretion in response to SERMs or AIs in older men is exacerbated by obesity.
“and this is exacerbated by obesity 108”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [108]
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- Authors
- Veldhuis, J. D., Liu, P. Y., Keenan, D. M., & Takahashi, P. Y.
- Affiliations
- Mayo Clinic (US)
- Woolcock Institute of Medical Research (AU)
- University of Virginia (US)
- Corresponding author
- Veldhuis, Johannes D.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2012-01-01
- Volume
- 302
- Issue
- 1
- Pages
- E117-E122
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3328086
- OpenAlex
- W2121845645
- Cited by
- 48
- References
- 42
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 5 · 2012: 1
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG023133, R01AG031763, R01AG023133, AG-031763)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050456, DK050456)
- National Center for Research Resources (UL1RR024150)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- recombinant human luteinizing hormone, LH pulsatility, testosterone secretion, age-related decline, GnRH antagonist, body mass index, healthy men
- MeSH terms
- Adolescent, Adult, Aged, Aging, Dose-Response Relationship, Drug, Hormone Antagonists, Humans, Infusions, Intravenous, Kinetics, Leydig Cells, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Middle Aged, Models, Biological, Obesity, Recombinant Proteins, Testosterone, Down-Regulation, Body Mass Index, Young Adult
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