Somatotropic dysregulation in old mammals

Area of Science:

• Endocrinology
• Neuroscience
• Aging Research

Background:

• Aging is associated with reduced spontaneous growth hormone (GH) secretion and diminished GH response to GH-releasing hormone (GHRH).
• This age-related decline in GH secretion affects various mammals, including humans and rats.

Purpose of the Study:

• To investigate the mechanisms underlying the reduced GH responsiveness to GHRH in aged mammals.
• To explore the roles of GHRH availability, pituitary GHRH receptor expression, and somatostatin in age-related GH hyposecretion.

Main Methods:

• In vivo and in vitro studies in aged and young rats.
• Measurement of GH secretion, GHRH response, pituitary adenylate cyclase activity, GHRH receptor number, and hypothalamic GHRH gene expression.
• Analysis of somatostatin expression and activity, and the influence of catecholaminergic and cholinergic neurons.

Main Results:

• Aged rats exhibit impaired pituitary responsiveness to GHRH, linked to diminished adenylate cyclase stimulation and reduced GHRH receptors on somatotrophs.
• Hypothalamic GHRH deficiency, indicated by reduced immunoreactivity and gene expression, contributes to the poor GH response.
• While GHRH hypofunction is a factor, it doesn't fully explain GH hyposecretion; increased somatostatin activity and altered neuronal regulation also play roles.

Conclusions:

• Age-related GH hyposecretion in mammals is multifactorial, involving hypothalamic GHRH deficiency, pituitary GHRH receptor changes, and dysregulation of somatostatin.
• Defects in catecholaminergic and cholinergic neuronal pathways likely contribute to the altered peptidergic neuron function observed in aging.