Somatotropic dysregulation in old mammals.
In old mammals, including humans, the spontaneous growth hormone (GH) secretory pattern is markedly reduced resulting in lower amounts of GH released over 24 h, and the GH response to administration of GH-releasing hormone (GHRH) is reduced. In agreement with these in vivo findings, an impaired responsiveness to GHRH is evident in the pituitary of old male and female rats in vitro, and this is linked with a diminished stimulation of adenylate cyclase by GHRH. The poor GH responsiveness to GHRH in old mammals, which in the rat is coupled to a defective number of GHRH receptors in the somatotrophs, is likely due to a primary deficiency of GHRH availability, as implied by the diminished GHRH immunoreactivity and gene expression in and GHRH release from the hypothalamus of old rats. Attempts have been made to stimulate the sluggish somatotrophic function in elderly humans and dogs using GHRH; in either species positive results were obtained though, overall, it would seem that the GHRH hypofunction does not entirely account for the GH hyposecretory state during ageing. Concerning somatostatin, although the expression of this peptide decreases with age in the rat hypothalamus, secretion and activity of this hormone is increased, resulting in an altered relationship between GHRH and somatostatin gene expression and secretion. It is likely that defects, especially in catecholaminergic and cholinergic neurons, are instrumental in altering specific peptidergic neurons. Reportedly, catecholamines induce GH release by stimulating GHRH neurons and inhibiting somatostatin-releasing neurons; acetylcholine stimulates GH release via muscarinic receptors, in this way inhibiting the action of somatostatin neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Müller
E E
EE
Department of Pharmacology, University of Milan, Italy.
Cella
S G
SG
Parenti
M
M
Deghenghi
R
R
Locatelli
V
V
De Gennaro Colonna
V
V
Torsello
A
A
Cocchi
D
D
D000375:Aging / Q000502:physiology*; D000818:Animals; D002395:Catecholamines / Q000502:physiology; D018678:Cholinergic Agents / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D008322:Mammals / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology; D051381:Rats; D013004:Somatostatin / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D002395:Catecholamines; D018678:Cholinergic Agents; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone