Growth hormone metabolism in hypopituitary subjects and young, middle-aged and elderly normal subjects
The purpose of these studies was to determine if human growth hormone (hGH) metabolism declines with advancing age. Twenty-two subjects' responses to the hGH provocative tests of exercise, L-DOPA, and insulin, hGH peak concentrations during sleep, and 24-hour integrated concentrations (ICGH) during a control period and following intramuscular administration of 0.168 U hGH/ kg Bw3/4/day were examined. Metabolic responses of 17 of these subjects were examined before and after hGH by measuring urinary excretion of creatinine, calcium, hydroxyproline and nitrogen.
Subjects were divided into the following groups: (I) 6 hypopituitary subjects 9 - 29 years old; (II) 4 men 23.,...29 years old; (III) 6 middle-aged men 35 - 51 years ol.d; and (IV) 6 elderly subjects 61 - 69 years old. Metabolic balance studies consisted of a 3 day adjustment period followed by a 5 day control period and a 5 day hGH administration period during which subjects were fed a constant, low hydroxyproline diet.
No hypopituitary subject exhibited a hGH concentration above 2 ng/ml at any time except following hGH administration, their mean ICGH increased from less than 2 ng/ ml to 5. 2 ng/ ml. Group II had the greatest mean hGH concentrations - 22 ng/ ml following exercise, 23 ng/ ml post L-DOPA, 30 ng/ ml post insulin, 21 ng/ ml during sleep and 3.5 ng/ ml control period 24-hour ICGH - to all tests except the ICGH, 3. 7 ng/ ml, following hGH administration. ICGH increased from less than 2 ng/ ml for all subjects in groups III and IV to 4.3 ng/ ml for one subject in group III and to a mean of 3. 7 ng/ ml for group IV. Mean hGH concentrations of 4 and 3 ng/ ml following exercise, . '5 and 11 ng/ ml post L-DOPA and 29 and 15 ng/ ml post insulin for groups III and IV respectively were intermediate between groups I and II. HGH concentrations above 5 ng/ ml were observed in only one subject in group III or IV during sleep.
Mean daily creatinine, calci1um, hydroxyproline and nitrogen excretion for group I.I and for creatinine and hydroxyproline excretion for groups I and IV were not statistically different during hGH administration from the control period. C4lcium excretion increased significantly from 2.91 to 6.31 mg/ kg BW/ day in group I and from 2.91 to 3.97 mg/ kg BW/ day in group IV following hGH administration. Nitrogen excretion decreased significantly from 137 to 99 ng/ kg BW/ day in group I and from 119 to 96 mg/ kg BW/ day in group IV following hGH administration.
These differences suggest a decline in hGH metabolism with age resulting from decreased circulating hGH, decreased response to hGH stimuli, fewer receptor sites at the tissue level for active hormone, or because of decreased hGH dependent-stimulation of somatomedin synthesis. Statistically different rates of calcium and nitrogen excretion during hGH administration associated with a statistical decrease in I I I circulating hGH in the elderly suggests the development of a type of functional hypopituitarism .as a consequence of aging.