Gender differences in secretory activity of the human somatotropic (growth hormone) axis
Abstract
Major gender differences exist in the prevalence and severity of various disease states, rates of organ-specific aging and drug and hormone metabolism. Increased understanding of the mechanistic bases for these important sex differences is likely to stimulate new prognostic, therapeutic and diagnostic insights over many succeeding decades. I will outline clinical data that bear on regulatory mechanisms that give rise to sex-based differences in the neuroendocrine activity of the human somatotropic (GH) axis. Such studies have important implications in both pubertal and gonadoprival states, such as aging and the menopause, when the sex-steroid milieu changes dramatically.
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Endogenous GH secretion in young women is consistently higher (typically twice as high) as in young men of similar age.
“The proposal that the sex difference in muscle mass and function might be due to sex differences in endogenous GH secretion (116) is refuted by the extensive and conclusive clinical evidence that endogenous GH secretion in young women is consistently higher (typically twice as high) as in young men of similar age (163–170).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [165]
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Self-citationGrowth Hormone, Insulin-Like Growth Factors, and the Skeleton
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Growth Hormone (GH)-Deficient Men Are More Responsive to GH Replacement Therapy Than Women1
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“The basal GH concentration (17), the 24-hour integrated GH secretion (16, 18 , 27), and the pituitary response to GHRH (19, 20) and arginine (28) are higher in premenopausal women than in men of a comparable age.”
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BackgroundRegulatory mechanisms of growth hormone secretion are sexually dimorphic.
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“Potential mechanisms underlying gender differences in GH secretion have been recently reviewed (16) and might include differences in GH clearance, in GHRH or somatostatin (SRIH) secretion, or in negative feedback at the level of the pituitary or hypothalamus by GH or insulin-like growth factor I (IGF-I).”
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“GH is secreted by the pituitary gland in a sex-dependent manner in both rodents (11) and humans (12).”
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“We (18) and others (44, 51) have demonstrated that GH secretion in adults is sexually dimorphic.”
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“prepubertal girls (33), here during the PO phase we find evidence for GH hypersecretion relative to IGF-I levels, thus strongly suggesting central actions of estrogen to stimulate GH production via one or more mechanisms (33).”
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“This is unfortunate because the regulatory mechanisms of GH secretion in humans are sexually dimorphic (7), and estrogen has well-known priming effects on GH-provocative tests in children and postmenopausal women (8–12).”
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“The sexually dimorphic pattern of growth hormone secretion in rats and humans has been shown to have physiological importance in the differential expression of sex-specific hepatic cytochrome P-450 drug-metabolizing enzymes (60, 62, 63).”
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“Similar GH regulation occurs in humans, where hepatic sex differences may prove relevant to pathophysiologies that vary with gender, such as differences in drug metabolism and incidence of certain diseases, as well as problems related to pregnancy (van den Berg et al. 1996; Veldhuis 1996; Jaffe et al. 1998).”
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“There are significant gender differences in GH secretion (3, 4).”
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“…animals, linear skeletal growth, body weight, and organ size have been shown to exhibit a strong dependence on either a pulsatile or continuous (‘‘male’’ or ‘‘female’’) temporal mode of GH release which are in turn related to higher and lower somatic growth rates, respectively (Veldhuis, 1996).”
BackgroundShah, N., Aloi, J., Evans, W. S., & Veldhuis, J. D. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.8.5881 · Cited by 46 · see citing works
Self-citationGender and age influence the relationship between serum GH and IGF‐I in patients with acromegaly
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Visceral Adipose Tissue Is Associated with Circulating High Affinity Growth Hormone-Binding Protein
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“H SECRETION is influenced by physical characteristics, such as age, sex, and adiposity (1, 2 ). Furthermore, GH plays a role in regulating fat mass by its lipolytic effect (3, 4). Studies from several research groups have emphasized the importance of regional adipose tissue distribution as a correlate of the metabolic…”
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Proposed Mechanisms of Sex-Steroid— Hormone Neuromodulation of the Human GH—IGF-I Axis
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“However, there is only a limited understanding of the exact neuroendocrine mechanisms that drive differential GH release in men and women (53).”
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Growth Hormone in Postmenopausal Women After Long-Term Oral Estrogen Replacement Therapy
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Self-citationDrug-disease interaction: Clinical consequences of inflammation on drugs action and disposition
Abdallah, Y. E. H., Chahal, S., Jamali, F., & Mahmoud, S. H. (2023) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2023.11137 · Cited by 30 · see citing works
“These findings of sex differences in CYP2B6 protein and activity raise the possibility that CYP2B6 and perhaps also CAR are regulated in a sex-dependent manner by human plasma Growth Hormone (GH) profiles (28, 29).”
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Self-citationGH responsiveness varies during the menstrual cycle
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Hormones and body size evolution in papionin primates
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Men with acromegaly need higher doses of octreotide than women
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“In conclusion, the IGF-I/GH ratio in female was a sexual dimorphism in the regulation of GH secretion pattern in healthy subjects [10, 11].”
BackgroundCombined Effect of Gender and Caloric Restriction on Liver Proteomic Expression Profile
Valle, A., Silvestri, E., Moreno, M., Chambery, A., Oliver, J., Roca, P., & Goglia, F. (2008) · Journal of Proteome Research · doi:10.1021/pr800086t · Cited by 19 · see citing works
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“A number of well-known factors had been reported to interfere with IGF-1 metabolism, such as age, gender, obesity, weight loss, malnutrition, or an altered glucose metabolism [22, 23, 42–44].”
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“Several clinical studies suggest that GH treatment can alter P450-dependent drug metabolism in humans [45].”
BackgroundHormonal Regulation of Liver Cytochrome P450 Enzymes
Waxman, D. J., & Chang, T. K. H. (2007) · Springer eBooks · doi:10.1007/0-387-27447-2_9 · Cited by 16 · see citing works
Chapter VIII Functional neuroanatomy of hypothalamic dopaminergic neuroendocrine systems
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“Previous studies suggest that androgens potentiate the effect of GH at the peripheral tissues but that oestrogens antagonize GH action at the peripheral level (Zachmann & Prader, 1970; Ho et al., 1987; van den Berg et al., 1996; Veldhuis, 1996; Blok et al., 1997).”
BackgroundSleep and Insulin-Like Growth Factors in the Cardiovascular Health Study
Shah, N. A., Rice, T., Tracy, D., Rohan, T. E., Bůžková, P., Newman, A. B., & Kaplan, R. C. (2013) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.3260 · Cited by 13 · see citing works
“Due to the major impact of gender on SWS, 25 sleep disordered breathing prevalence, 26 and on the GH/IGF axis, 27-29 we present our primary analyses in a gender stratified manner.”
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“All of these components of the GH–IGF axis are influenced by sex steroids (androgens and estrogens) (Veldhuis 1996).”
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“Furthermore, there is quite robust evidence in the literature to suggest that endogenous estrogens play a major role in increased GH secretion in women compared with men [39].”
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Octreotide long-acting repeatable for acromegaly
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“42 Biermasz NR, Pereira AM, Frolich M, Romijn JA, Veldhuis JD, Roelfsema F. Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly.”
BackgroundBackground Gene Expression in Rat Kidney: Influence of Strain, Gender, and Diet
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“One example is the gender-specific secretion patterns of growth hormone by the pituitary gland which has been demonstrated in both rodents (Jansson et al., 1985) and humans ( Veldhuis, 1996 ).”
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Neuroendocrine facets of human puberty
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Effect of growth hormone on bone status in growth hormone-deficient adults
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Self-citationPseudoacromegaly and Hyperinsulinemia: A Possibility of Premature Atherosclerosis?1
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Insulin-like Growth Factor 1 Level and Its Relating Factor in Korean Healthy Adults
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mahdavian, A., & Kormi‐Nouri, R. (2008) · Journal of Applied Sciences · doi:10.3923/jas.2008.1055.1060 · Cited by 4 · see citing works
Impact of Chronic Training on Pituitary Hormone Secretion in the Human
Veldhuis, J. D., & Yoshida, K. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-314-5_4 · Cited by 4 · see citing works
Self-citationde Vries, W. R., Koppeschaar, H. P. F., Bol, E., et al. (2000) · Journal of Endocrinological Investigation · doi:10.1007/bf03343754 · Cited by 4 · see citing works
GH-Deficient Men Are More Responsive to GH Replacement Therapy Than Women—Author’s Responsec
Burman, P., Johansson, A. G., Engström, B. E., et al. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4288-3 · Cited by 4 · see citing works
Veldhuis, J. D. (2000) · Rejuvenation Research · doi:10.1089/rej.1.2000.3.269 · Cited by 4 · see citing works
Self-citationTrarbach, E. B., Jorge, A. A. L., Duarte, F. H. G., et al. (2016) · Pituitary · doi:10.1007/s11102-016-0779-1 · Cited by 3 · see citing works
Growth Hormone Releasing Hormone
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Jamieson, B. B. (2025) · Journal of Neuroendocrinology · doi:10.1111/jne.70117 · Cited by 2 · see citing works
“30, 31 This sex difference appears to be mediated by oestrogen, as pulse amplitude rises across the menstrual cycle in parallel with increasing oestrogen levels 30 (Figure 1B).”
Rabelink, N. M., Peeters, G. M. E. E., van Schoor, N. M., Drent, M. L., & Lips, P. T. A. M. (2011) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0b013e31820367b3 · Cited by 1 · see citing works
“32 Cortisol (nmol/L)b 98 31 (20) 897 32 (23) −1.”
Role of Pulsatility in Hormonal Action
Murray‐McIntosh, R. P. (1998) · Comprehensive physiology · doi:10.1002/cphy.cp070119 · Cited by 1 · see citing works
Sex-Steroid Hormone Modulation of the Tripeptidyl Control of the Human Somatotropic Axis
Veldhuis, J. D., Evans, W. S., Anderson, S. M., & Bowers, C. Y. (2002) · Rejuvenation Research · doi:10.1089/109454502317629327 · Cited by 1 · see citing works
“Consequently, clinical studies of neuroendocrine regulation rely on serial measurements of plasma GH concentrations as a window to hypothal-amo-pituitary control 33–35 (Fig.”
Self-citationEffects of Aging on Gonadotropin/Ovarian and Growth Hormone/Ovarian Relationships in Normal Women
Evans, W. S., Brill, K. T., & Veldhuis, J. D. (2004) · Principles of Gender-Specific Medicine · doi:10.1016/b978-012440905-7/50386-8
Self-citationRapporto tra acromegalia e neoplasia: fantasia o realtà?
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The Growth Hormone IGF-I Axis and Menopause
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Influence of Gonadal Function on GH Secretion
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Impact of Chronic Training on Pituitary Hormone Secretion in Humans
Veldhuis, J. D., & Yoshida, K. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-030-33376-8_4
Self-citationImpact of Chronic Training on Pituitary Hormone Secretion in the Human
Veldhuis, J. D., & Yoshida, K. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-016-2_4
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Role of Pulsatility in Hormonal Action
Murray‐McIntosh, R. P. (1997) · Comprehensive physiology · doi:10.1002/j.2040-4603.1997.tb01443.x
“…metabolic clearance rate of growth hormone in women; however, without measurements of volume distribution, growth hormone-binding protein (GHBP) concentration, and other potential influences on clearance, the high baseline of growth hormone cannot be attributed to a longer half-life in women (181).”
- Authors
- Veldhuis, J. D.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Veldhuis, Johannes D
- ORCID
- Veldhuis, Johannes D
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-03
- Volume
- 134
- Issue
- 3
- Pages
- 287-295
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2136396730
- Cited by
- 102
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 3 · 2018: 1 · 2016: 1 · 2015: 1 · 2013: 4 · 2012: 1
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California HIV/AIDS Research Program
- National Institutes of Health (5k04hd000634-02, 5p30dk038942-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 38942)
- National Center for Research Resources (RR 00847, M01RR000847)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (1-K04-HD-00634)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- sex differences, growth hormone, somatotropic axis, neuroendocrine regulation, puberty, gonadectomy, aging, menopause, sex steroids, hormone secretion
- MeSH terms
- Female, Humans, Kinetics, Male, Menstrual Cycle, Neurosecretory Systems, Pulsatile Flow, Sex Characteristics, Growth Hormone, Growth Hormone-Releasing Hormone
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