Predictors of Growth Hormone Secretion in Aging

Summary: Growth hormone again

Interestingness: 2

Paper by Mark L Hartman, Jody L Clasey, Arthur Weltman and Michael O Thorner in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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Growth hormone (GH) secretion goes down with age at an inversely logarithmic rate. It is almost down all the way by time we are in our 30s. This may not be due to age alone though, since there are high correlations between integrated GH concentration and each of BMI, percentage body fat and fitness, as measured by oxygen consumption, especially in men (in women the effect does not reach the magic 0.05).

Most of the reasons listed for the decrease we've seen before already (growth hormone papers). Some that I haven't:

• GH secretions four times higher during stage 3 and 4 sleep. Deep sleep goes to the shit with age.
• Possible path by which high fat reduces GH: high free insulin-like growth factor 1 (IGF-1). But then they quote study showing inverse correlation between free IGF-1 and visceral fat.

In their own studies, they find correlations between integrated GH concentration and each of abdominal visceral fat, fasting insulin and IGF-1, independent of age, sex, total body fat mass, percentage fat, 24 hour mean estradiol and testosterone, and peak oxygen uptake, in a group of 40 people in their 20s and 62 in the 57-80 year old range. Also, a high correlation between the combination of age and sex with IGF-1.

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Abstract follows:

Growth hormone (GH) secretion decreases progressively after mid-puberty in both men and women. This decrease occurs predominantly before age 40-50 and affects both daytime and nocturnal GH secretion. A reduction in the amplitude of GH secretory pulses accounts for the majority of the reduction in GH secretion. With aging, changes in hypothalamic function may occur that result in decreased GH secretion. These changes may include decreased secretion of GH-releasing hormone and/or the putative natural ligand for the GH secretagogue receptor or an increase in somatostatin release. Multiple physiological factors have been reported to regulate GH secretion including sleep, body composition (% body fat and amount of abdominal visceral fat), aerobic physical fitness and serum concentrations of insulin-like growth factor-I (IGF-I), gonadal steroids and insulin. Changes in these factors with aging may contribute to the reduction in GH secretion observed in older adults. However, these physiological predictors of GH secretion are not independent of one another and the relative importance of these factors in the regulation of GH secretion is not known. Preliminary evidence suggests that the amount of abdominal visceral fat and fasting serum concentrations of insulin and IGF-I are the most important predictors of 24-hour GH release in healthy adults, independent of age and gender. Bi-directional feedback between these three factors and GH secretion may account for the strong relationships observed.

Network-Like Facets of Neuroendocrine Aging in the Human: Specific Disruption of Feedback and Feedforward Linkages Within the Aging Somatotropic ...

Full title, since it didn't fit: Network-Like Facets of Neuroendocrine Aging in the Human: Specific Disruption of Feedback and Feedforward Linkages Within the Aging Somatotropic, Gonadotropic, and Corticotropic Axes in Men and Women

Summary: Lots of facts about growth hormone, leutinising hormone, follicle-stimulating hormone and gonadotropin-releasing hormone, with very little cohesion.

Interestingness: 3

Paper by Johannes D Veldhuis in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, Spring 2000.


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This is another long review paper by Veldhuis mainly about growth hormone (GH) and its friends, even though its supposedly about the interaction between different hormonal axes. It has 266 references. It's too much information to summarise. I'll jot some notes. A lot of the same information as in Veldhuis's previous paper is covered as well as in all the other GH papers. I'll skip bits that I think are repeated. A lot of the graphs presented don't look very convincing. They tend to have around 10 people per group, so the curves look like they could change easily.

Newer data says more GH secreted by women than men, and decline with aging is half as slow.
Secretion pulses more irregular and lower in older people for GH, leutinising hormone (LH), insulin and prolactin. Follicle-stimulating hormone (FSH) secretion pulse and base go up.
Intra-venous gonadotropin releasing hormone (GnRH) pulses normalised LH secretion in older men.

Inferenced mechanisms mentioned:

• Lower endogenous growth hormone-releasing hormone (GHRH) secretion and/or lower growth hormone releasing peptide (GHRP) effect could explain loss of GH secretory pulse.
• Evidence for too much somatostatin and GHRH deficiency. Neither alone enough.
• Partial GnRH deficiency and Leydig-cell steroidogenic defect both exist, and the latter is not fixed by external GnRH.

They do some computer models of the GnRH-LH-T axis and from those they like the following hypotheses for the loss of synchrony between LH and T release in older men:

• Lower feed-forward drive of T synthesis by Leydig cells.
• Same, plus lowered negative-feedback by T of GnRH and LH release.

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Abstract follows:

The present update highlights the impact of age on dynamic regulatory changes arising singly and multiply within several prototypical neuroendocrine axes in the human. A neuroendocrine axis is viewed here as a homeostatic unit maintained by multivalent interactions or network-like integration among CNS-hypothalamic, pituitary, and target-tissue sites; for example, the GHRH/somatostatin-GH-IGF-I, GnRH-LH-sex-steroid and CRH/AVP-ACTH-cortisol feedback-controlled axes. Homeostatic control is driven by (time-lagged) interglandular signaling and dose-sensitive interfaces. According to this broader perspective, a neuroendocrine system operates as an interdependent ensemble of reciprocally communicating control nodes. This dynamic precept provides a foundation for identifying among the earliest vivid features of signaling disruption within the somatotropic, gonadotropic, and corticotropic (as well as insulinotropic) axes in healthy aging men and women. Internodal linkages likely deteriorate further in the face of acute or chronic illness, medication use, systemic stress and/or hospitalization, resulting at times in overt failure of neuroglandular output. This extended concept offers a notion of neuroendocrine axis frailty as a precursor to frank endocrinesystem disability in aging. Such a framework also confers the expectation that pluri- or multiaxis disruption (e.g., combined somatotropic and gonadal) would further adversely impact homeostatic vigor in aging individuals.