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Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism

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Abstract

There is evidence suggesting that androgens influence GH secretion in man. Our aim was to verify whether the GH releasable pool is preserved and influenced by testosterone replacement in male hypogonadism. To this goal, in eight male hypogonadal patients (HP, age 32.2±5.0 yr; Body Mass Index 23.9±1.1 kg/m2) before and after 3 months testosterone therapy, we studied the GH response to GHRH (1 μg/kg iv) alone and combined with pyridostigmine (PD, 120 mg po), a cholinesterase inhibitor which likely inhibits hypothalamic somatostatin release allowing exploration of the maximal somatotrope secretory pool. Sixteen normal subjects (NS, age 30.1 ±3.5 yr; Body Mass Index 22.5±1.8 kg/m2) were studied as controls. The GH response to GHRH in HP was similar to that in NS (AUC, mean±SE: 1238±362 vs 1018±182 μg/L/h). PD potentiated to the same extent the GH response to GHRH in both groups (2092±807 and 2840±356 μg/L/h). After three month testosterone therapy, in HP the GH responses to GHRH alone (1352±612 μg/L/h) and combined with PD (1948±616 μg/L/h) were unchanged. Also IGF-I levels in HP were similar to those in NS (222±42 vs 210.6±55.8 μg/L) and were unchanged during testosterone replacement (280±31 μg/L). As androgens have been reported to modulate sympathoadrenal activity in the rat, both before and during testosterone replacement, we also measured plasma catecholamine levels. Basal NE (p< 0.05) but not E levels were lower in HP than in NS; testosterone restored basal NE levels to normal without affecting basal E. Δ absolute increase of NE and E (p<0.05 and 0.01 vs baseline, respectively) after PD in HP were similar to those in NS and were unchanged during testosterone replacement. In conclusion, these results demonstrate that the GH releasable pool is preserved in male hypogonadism. As in this condition a reduction of spontaneous GH secretion has been reported, it could be due to neurosecretory dysfunction but not to pituitary impairment. Subtle alterations of sympathoadrenal activity seem to be present in male hypogonadism and reversed by testosterone replacement.

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Authors and Affiliations

  1. Dipartimento di Medicina Interna, Cattedra di Endocrinologia, University of Modena, Italy

    G. Del Rio, C. Carani, A. Velardo, G. Zizzo, F. Coletta & P. Marrama

  2. Dipartimento di Fisiopatologia Clinica, Cattedra di Endocrinologia, University of Torino, C.so A.M. Dogliotti 14, 10126, Torino, Italy

    M. Procopio & Ezio Ghigo M.D.

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  1. G. Del Rio
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  2. C. Carani
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Del Rio, G., Carani, C., Velardo, A. et al. Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism. J Endocrinol Invest 18, 690–695 (1995). https://doi.org/10.1007/BF03349790

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