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Cholinergic Receptor Activation by Pyridostigmine Restores Growth Hormone (GH) Responsiveness to GH Releasing Hormone Administration in Obese Subjects: Evidence for Hypothalamic Somatostatinergic Participation in the Blunted GH Release of Obesity^*

Departments of Physiology (CD.) and Medicine (F.F.C.), Hospital General Galicia Endocrine Section, University of Compostela Santiago de Compostela, Spain
The Hospital Xeral Lugo, Endocrine Unit (F.C.) Lugo, Spain

Address all correspondence and requests for reprints to: Dr. Carlos Dieguez, P.O. Box 563, Santiago de Compostela, Spain.

GH secretion in response to provocative stimuli is decreased in obese individuals. However, the precise mechanism causing this decrease is unknown. In an attempt to determine if reduced cholinergic stimulation accounts for the decreased GH secretion, we studied the effect of enhanced cholinergic tone induced by pyridostigmine on GHRH-stimulated GH secretion in a group of seven obese and seven normal subjects.

When GHRH (100 µg, iv) was administered after placebo in the obese group, mean plasma GH rose from 0.5 ± (0.1 (±SE) to 3.6 ± 1.5 µg/L at 30 min. When the same obese subjects were given GHRH 60 min after pyridostigmine administration (120 mg, orally), the mean plasma GH level rose from 1.8 ± 0.6 to 21.0 ± 7.5 µg/L at 30 min. The responses to placebo and pyridostigmine were significantly different at 15, 30, 45, 60, and 90 min. In the normal subjects, a similar dose of GHRH induced a GH peak of 24.3 ±7.1 µg/L, and the GHRH-stimulated peak was significantly higher (56.2 ± 16.8 µg/L) after pyridostigmine administration. To study the effect of pyridostigmine alone six other obese and six other normal subjects were tested with pyridostigmine or placebo on different days. In the normal subjects the mean peak plasma GH level after pyridostigmine was 12.5 ± 3.1 µg/L, and in the obese sugjects it was 4.6 ± 1.3 µg/h. Thus, pyridostigmine potentiated the action of GHRH, rather than merely being additive.

We conclude that pyridostigmine stimulates GH secretion in obese as well as normal subjects, although the response was less in the former group. Pyridostigmine potentiates the response to GHRH in both groups, but again, the response was less in the obese subjects. These results suggest that the impaired somatotroph responsiveness in obese subjects may be due to chronically decreased hypothalamic cholinergic tone, resulting in enhanced somatostatinergic tone

^* This work was supported by Grants FISss 88-0812 and 88-0818 and Xunta de Galicia 609027/5380, and 6092275450.

Received May 16, 1988.

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