Comparative Effect of Clonidine and Growth Hormone (GH)-Releasing Hormone on GH Secretion in Adult Patients on Chronic Glucocorticoid Therapy
Summary Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic agonist which increases G H secretion acting at the hypothalamic level with an unknown mechanism, on G H secretion in seven adult patients (3M, 4F) with non endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a blunted G H response to G H R H (GH peak 8.3 + 3 ug/L) with respect to normal subjects (GH peak 19.3 ± 2 . 4 ug/L). The G H responses to clonidine were also blunted (p < 0.05) in steroid-treated patients (GH peak 5.8 + 2.8 ug/L) with respect to normal subjects (GH peak 17.6 + 2.3 u.g/L). No significant differences between the G H responses to G H R H and clonidine were observed either in steroid-treated or in normal subjects. Clonidine is not able to enhance G H secretion similar to G H R H in patients chronically treated with steroids. It can be hypothesized that clonidine does not elicit G H secretion decreasing hypothalamic somatostatin tone. Key words Clonidine — Growth Hormone (GH) — GHReleasing Hormone — Somatostatin — Glucocorticoids — Immunosuppression — Adrenergic System
uchi and Mashimo 1969; Hotta, Shibasaki, Masuda, Imaki, Sugino, Demura, Ling and Shizume 1988; Giustina, Doga, Bodini, Girelli, Legati, Bossoni and Romanelli 1990a). G H synthesis and secretion are regulated by the hypothalamic peptides GH-releasing hormone (GHRH), with an excitatory role, and somatostatin, with an inhibitory role (Dieguez, Page and Scanlon 1988). Recently, studies in rat and man have shown that the inhibitory effects of glucocorticoids on G H secretion may be due to an enhanced hypothalamic somatostatin tone (Giustina, Girelli, Doga, Bodini, Bossoni and Romanelli 1990b; Wehrenberg, Janowski, Piering, Culler and Jones 1990). Clonidine is a central alpha-2-adrenergic receptor agonist and is a potent G H secretagogue in man (Lal, Tolis, Martin, Brown and Guyda 1975; Gil-Ad, Tropper and Laron 1979) and animals (Miki, Ono and Shizume 1984). The stimulatory effect of clonidine on G H secretion has been suggested to depend on an enhancement of hypothalamic G H R H release into the hypophyseal portal blood both in the rat (Miki, Ono and Shizume 1984) and in humans (Alba-Roth, Losa, Spiess, Schopohl, Muller and von Werder 1989; Loche, Puggioni, Fanni, Cella, Muller and Pintor 1989). However, an alpha-adrenergic-mediated inhibition of the hypothalamic somatostatin release has also been postulated (Valcavi, Dieguez, Page, Zini, Casoli, Portioli and Scanlon 1988). The aim of our study was to evaluate the effects of clonidine and G H R H on G H secretion in adult patients receiving daily immunosuppressive glucocorticoid treatment for non endocrine diseases. Subjects and Methods
Introduction Glucocorticoids cause impaired somatic growth in animals {Hodges and Vernikos 1958) and in man (Blodgett, Burgin, lezzoni, Gribetz and Talbot 1956; Solomon and Schoen 1976). Blunted G H responses to several pharmacological stimuli in normal subjects after administration of supraphysiological doses of glucocorticoids and in patients with Cushing's disease have been observed {Nakagawa, Hori-
Horm. metab. Res. 24 (1992) 240 -243 © GeorgThieme Verlag Stuttgart-New York
Subjects We studied seven adult non obese patients with non endocrine diseases (4 males and 3 females; age 39 + 4 yrs; body mass index 25 + 1 kg/m ) under chronic immunosuppressive steroid treatment from at least 1 year (mean 3.5 ± SEM 1 yrs). Four of them were affected by systemic lupus erythematosus, two by polymialgia rheumatica and one by scleroderma. All the patients were in good general condition with normal liver and kidney function. None of the patients was taking any drugs other than prednisone (mean dose
Received: 23 May 1991
Accepted: 30 Sept. 1991
Downloaded by: National University of Singapore. Copyrighted material.
A. Giustina , M. Grazia Buffoli, A. Rosa Bussi , M. Doga , Angela Girelli , G. Pizzocolo , A. Pozzi and W. B. Wehrenberg Cattedra di Clinica Medica and Chimica, University of Brescia, Italy 3 Department of Health Sciences, University of Wisconsin, Milwaukee, U. S. A.
Horm. metab. Res. 24 (1992)
Fig. 1 Mean±SEM (a) absolute GH levels (ug/L) and (b) GH area under the curves (AUCs; u.g/L x 120 min) after GHRH in eleven normal adult subjects (open symbols) and in seven adult subjects receiving glucocorticoid therapy bid (filled symbols). *p
Summary Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic agonist which increases G H secretion acting at the hypothalamic level with an unknown mechanism, on G H secretion in seven adult patients (3M, 4F) with non endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a blunted G H response to G H R H (GH peak 8.3 + 3 ug/L) with respect to normal subjects (GH peak 19.3 ± 2 . 4 ug/L). The G H responses to clonidine were also blunted (p < 0.05) in steroid-treated patients (GH peak 5.8 + 2.8 ug/L) with respect to normal subjects (GH peak 17.6 + 2.3 u.g/L). No significant differences between the G H responses to G H R H and clonidine were observed either in steroid-treated or in normal subjects. Clonidine is not able to enhance G H secretion similar to G H R H in patients chronically treated with steroids. It can be hypothesized that clonidine does not elicit G H secretion decreasing hypothalamic somatostatin tone. Key words Clonidine — Growth Hormone (GH) — GHReleasing Hormone — Somatostatin — Glucocorticoids — Immunosuppression — Adrenergic System
uchi and Mashimo 1969; Hotta, Shibasaki, Masuda, Imaki, Sugino, Demura, Ling and Shizume 1988; Giustina, Doga, Bodini, Girelli, Legati, Bossoni and Romanelli 1990a). G H synthesis and secretion are regulated by the hypothalamic peptides GH-releasing hormone (GHRH), with an excitatory role, and somatostatin, with an inhibitory role (Dieguez, Page and Scanlon 1988). Recently, studies in rat and man have shown that the inhibitory effects of glucocorticoids on G H secretion may be due to an enhanced hypothalamic somatostatin tone (Giustina, Girelli, Doga, Bodini, Bossoni and Romanelli 1990b; Wehrenberg, Janowski, Piering, Culler and Jones 1990). Clonidine is a central alpha-2-adrenergic receptor agonist and is a potent G H secretagogue in man (Lal, Tolis, Martin, Brown and Guyda 1975; Gil-Ad, Tropper and Laron 1979) and animals (Miki, Ono and Shizume 1984). The stimulatory effect of clonidine on G H secretion has been suggested to depend on an enhancement of hypothalamic G H R H release into the hypophyseal portal blood both in the rat (Miki, Ono and Shizume 1984) and in humans (Alba-Roth, Losa, Spiess, Schopohl, Muller and von Werder 1989; Loche, Puggioni, Fanni, Cella, Muller and Pintor 1989). However, an alpha-adrenergic-mediated inhibition of the hypothalamic somatostatin release has also been postulated (Valcavi, Dieguez, Page, Zini, Casoli, Portioli and Scanlon 1988). The aim of our study was to evaluate the effects of clonidine and G H R H on G H secretion in adult patients receiving daily immunosuppressive glucocorticoid treatment for non endocrine diseases. Subjects and Methods
Introduction Glucocorticoids cause impaired somatic growth in animals {Hodges and Vernikos 1958) and in man (Blodgett, Burgin, lezzoni, Gribetz and Talbot 1956; Solomon and Schoen 1976). Blunted G H responses to several pharmacological stimuli in normal subjects after administration of supraphysiological doses of glucocorticoids and in patients with Cushing's disease have been observed {Nakagawa, Hori-
Horm. metab. Res. 24 (1992) 240 -243 © GeorgThieme Verlag Stuttgart-New York
Subjects We studied seven adult non obese patients with non endocrine diseases (4 males and 3 females; age 39 + 4 yrs; body mass index 25 + 1 kg/m ) under chronic immunosuppressive steroid treatment from at least 1 year (mean 3.5 ± SEM 1 yrs). Four of them were affected by systemic lupus erythematosus, two by polymialgia rheumatica and one by scleroderma. All the patients were in good general condition with normal liver and kidney function. None of the patients was taking any drugs other than prednisone (mean dose
Received: 23 May 1991
Accepted: 30 Sept. 1991
Downloaded by: National University of Singapore. Copyrighted material.
A. Giustina , M. Grazia Buffoli, A. Rosa Bussi , M. Doga , Angela Girelli , G. Pizzocolo , A. Pozzi and W. B. Wehrenberg Cattedra di Clinica Medica and Chimica, University of Brescia, Italy 3 Department of Health Sciences, University of Wisconsin, Milwaukee, U. S. A.
Horm. metab. Res. 24 (1992)
Fig. 1 Mean±SEM (a) absolute GH levels (ug/L) and (b) GH area under the curves (AUCs; u.g/L x 120 min) after GHRH in eleven normal adult subjects (open symbols) and in seven adult subjects receiving glucocorticoid therapy bid (filled symbols). *p
