Aspects of the neuroendocrine control of growth hormone secretion in ageing mammals.
In aged animals and humans the pulsatile secretion of growth hormone (GH), the mean amounts of GH released over 24 h, and the response of GH to the administration of GH-releasing hormone (GHRH) are lower than in young adults. Pituitary somatotrophic cells in old male and female rats show an impaired responsiveness to GHRH, and the reduced secretion of GH in vitro is linked with a diminished stimulation of adenylate cyclase by GHRH. Pretreatment with GHRH in vivo decreases the high basal adenylate cyclase activity in old male rats. This pretreatment does not affect the rise of adenylate cyclase concentration in these rats that is subsequently induced by GHRH administration in vitro. However, it does induce a small rise in adenylate cyclase concentration in old female rats. In young rats of either sex the same GHRH schedule does not alter adenylate cyclase activity, but it does reduce the effectiveness of subsequent acute exposure to GHRH to stimulate enzymatic activity. Short-term administration of GHRH in some aged subjects increases the response of GH to a subsequent acute challenge with GHRH. However, primary or secondary alterations in somatotrophic cells are also present in aged mammals, such as a reduction in the number of GH-immunoreactive structures or post-receptor alterations. In aged rats, major alterations in brain neurotransmitters and neuropeptides are present in hypothalamic and extrahypothalamic structures, especially in catecholaminergic and acetylcholinergic neurones. These alterations are probably due to defects in neurosecretory GHRH and somatostatin neurones. GHRH synthesis is impaired in the hypothalamus of senescent male rats, as shown by a reduction in GHRH mRNA levels and GHRH-like immunoreactivity. Although the expression of somatostatin seems to decrease 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. Catecholamines induce GH release in most animal species by stimulating GHRH neurones and inhibiting somatostatin-releasing neurones. Acetylcholine stimulates GH release via muscarinic receptors, and thus inhibits the effect of somatostatin neurones. In male rats of various ages, except very young rats, systemic administration of pilocarpine, an agonist of muscarinic receptors, potentiates the GH response to GHRH during the entire lifespan.(ABSTRACT TRUNCATED AT 400 WORDS)
Müller
E E
EE
Department of Pharmacology, School of Medicine, University of Milan, Italy.
Cella
S G
SG
De Gennaro Colonna
V
V
Parenti
M
M
Cocchi
D
D
Locatelli
V
V
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D002648:Child; D004285:Dogs; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D008322:Mammals / Q000502:physiology*; D009490:Neurosecretory Systems / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D051381:Rats
D018377:Neurotransmitter Agents; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone