Anatomy and Physiology of the Hypothalamic-Pituitary-Gonadal (HPG) Axis

Dwyer, Andrew A.; Quinton, Richard

doi:10.1007/978-3-319-99817-6_43

Cited by 28 publications

(23 citation statements)

References 29 publications

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“…Our findings are largely consistent with results from clinical trials [14,46], and some [12,22,47], but not all [13], cross-sectional analyses. The slightly elevated testosterone concentrations in men with higher levels of physical activity may be due to elevated SHBG concentrations, which increases the half-life of testosterone and may also result in an increase in testosterone production via the hypothalamic-pituitary-gonadal axis [48]. Findings from other studies are inconclusive [10, 12-15, 18, 46], but power was generally limited.…”

Section: Discussionmentioning

confidence: 99%

Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank

Watts

Pérez-Cornago

Allen

et al. 2021

Cancer Causes Control

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Purpose Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI). Methods Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI. Results The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI. Conclusion Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.

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Section: Discussionmentioning

confidence: 99%

Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank

Watts

Pérez-Cornago

Allen

et al. 2021

Cancer Causes Control

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“…20 In men, testosterone is primarily synthesized by the testes and serum concentrations of free testosterone are regulated by the hypothalamic-pituitary-gonadal (HPG) axis. 21 In postmenopausal women, testosterone is primarily synthesized peripherally from androstenedione and other androgen precursors as well as by the ovaries, and the HPG axis is thought to have little direct effect in the regulation of testosterone concentrations. 22,23 In both sexes, sex hormone-binding globulin (SHBG) is primarily synthesized by the liver and is secreted into the bloodstream, where it tightly binds to sex hormones and modulates their bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Prospective analyses of testosterone and sex hormone‐binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank

Watts

Pérez-Cornago

Tsilidis

et al. 2021

Intl Journal of Cancer

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We investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank. Risk was estimated using multivariable-adjusted Cox regression in up to 182 608 men and 122 112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within 2 years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements.We accounted for multiple testing using the false discovery rate. In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase = 1.35, 95% CI 1.14-1.61 and 1.10, 1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/ L = 2.45, 1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer

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“…For example, Fig. 5C shows the feedback loop between gonadotrophs in the anterior pituitary and the estrogen-producing granulosa cells of the ovary (fortuitously obtained from female perigonadal fat), a classical example of hormonal feedback control that is evolutionarily conserved across vertebrates (Dwyer and Quinton, 2019). Consistent with this scheme, mouse lemur gonadotrophs expressed two highly-conserved gonadotropins, follicle stimulating hormone (FSH, a dimer of FSHB and CGA) and luteinizing hormone (LH, LHB/CGA dimer), which target granulosa cells through the corresponding receptors FSHR and LHCGR.…”

Section: Resultsmentioning

confidence: 99%

An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome

Liu

Ezran

Wang

et al. 2021

Preprint

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Hormones coordinate long-range cell-cell communication in multicellular organisms and play vital roles in normal physiology, metabolism, and health. Using the newly-completed organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), we have systematically identified hormone-producing and -target cells for 87 classes of hormones, and have created a browsable atlas for hormone signaling that reveals previously unreported sites of hormone regulation and species-specific rewiring. Hormone ligands and receptors exhibited cell-type-dependent, stereotypical expression patterns, and their transcriptional profiles faithfully classified the discrete cell types defined by the full transcriptome, despite their comprising less than 1% of the transcriptome. Although individual cell types generally exhibited the same characteristic patterns of hormonal gene expression, a number of examples of similar or seemingly-identical cell types (e.g., endothelial cells of the lung versus of other organs) displayed different hormonal gene expression patterns. By linking ligand-expressing cells to the cells expressing the corresponding receptor, we constructed an organism-wide map of the hormonal cell-cell communication network. The hormonal cell-cell network was remarkably densely and robustly connected, and included classical hierarchical circuits (e.g. pituitary → peripheral endocrine gland → diverse cell types) as well as examples of highly distributed control. The network also included both well-known examples of feedback loops and a long list of potential novel feedback circuits. This primate hormone atlas provides a powerful resource to facilitate discovery of regulation on an organism-wide scale and at single-cell resolution, complementing the single-site-focused strategy of classical endocrine studies. The network nature of hormone regulation and the principles discovered here further emphasize the importance of a systems approach to understanding hormone regulation.

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Anatomy and Physiology of the Hypothalamic-Pituitary-Gonadal (HPG) Axis

Cited by 28 publications

References 29 publications

Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank

Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank

Prospective analyses of testosterone and sex hormone‐binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank

An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome

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