Acute effects of cortisone
hormone-releasing Andrea Giustina, Mauro
growth hormone response to hormone in normal adult subjects
acetate on
growth
Doga, Corrado Bodini, Angela Girelli, Fabio Legati, Simonetta Bossoni and Giuseppe Romanelli
Cattedra di Patología
Spéciale Medica, University of Brescia, Italy
Abstract Glucocorticoids have been shown
to inhibit GH secretion in normal man when administered in large amounts for several days. The aim of our study was 1. to investigate the acute effects of a single dose of glucocorticoids on GH secretion in normal man; 2. to look at the relationship between the increase in serum cortisol concentration and GH response to the stimuli. Six healthy volunteers received on three occasions in random order an iv injection of GHRH (1-29) NH2, 100 \g=m\g,alone or 60 min after oral administration of either 25 or 50 mg of cortisone acetate. Mean stimulated GH levels, GH peak and integrated GH concentration were significantly lower after GHRH plus cortisone 25 mg than after GHRH alone. Mean GH levels at 15 and 30 min after GHRH injection and the peak GH level showed a further decrease after GHRH plus cortisone 50 mg. We conclude that acute administration of pharmacological doses of glucocorticoids is able to inhibit GH response to GHRH, probably through enhancement of endogenous somatostatin release. Moreover, this pharmacological effect of glucocorticoids seems to be dose-dependent and thus directly related to serum cortisol concentrations.
known to have reduced GH response to these stim¬ uli, and in some patients with acromegaly GH re¬ sponses to GHRH are decreased by pharmacolog¬ ical doses of glucocorticoids (8-9). On the other hand, several studies have reported that glucocorticoids enhance GH release by cul¬ tured rat and human pituitary somatotropes (10), GH gene transcription (11), and GHRH receptor synthesis (12). In adrenalectomized rats the GH response to GHRH has been clearly shown to depend on the presence of physiological glucocorticoid levels (13). Moreover, GH deficiency in pa¬ tients with idiopathic adrenocorticotropin defi¬ ciency resolves during glucocorticoid replacement
(14).
Recently, it has been suggested that the contra¬ dictory evidence from in vitro and in vivo studies regarding the effects of glucocorticoids on GH se¬ cretion could be due to in vivo glucocorticoid en¬ hancement of hypothalamic somatostatin release (15).
Glucocorticoids have long been known to interfere with normal growth, their administration leading to growth retardation in animals (1) as well as in man (2). The role played by glucocorticoids in the regulation of GH secretion is still unclear. Administration of supraphysiological doses of glucocorticoids is able to blunt GH response to var¬ ious pharmacological and physiological stimuli and to diminish GH production rate in normal man (3-7). Moreover, patients with Cushing's disease are
All the cited studies, both those concerning ad¬ ministration of large glucocorticoid doses to normal man and those concerning hypo- or hyperadrenal subjects, did not investigate the relation¬ ship between acute rises in serum cortisol concen¬ trations and pituitary GH responsiveness to the stimuli. Therefore, the aim of our study was 1. to inves¬ tigate the acute effects of a single dose of gluco¬ corticoids on GH secretion in normal man; 2. to look at the relationship between the increase in
serum cortisol concentrations obtained with two different doses of glucocorticoids and the GH re¬ sponse to GHRH administration.
40
30J
Subjects and Methods We studied 6 healthy adult volunteers with no family his¬ tory of endocrine or metabolic disease, all doctors or med¬ ical students, 4 males and 2 females, age range 22-25 with years, body mass index ranging from 18 to 24 normal thyroid and adrenal function. None of the sub¬ jects was taking any drug at the start of the study and all subjects were examined on three different occasions with at least 7-day intervals. The study protocol was approved by the Local Ethical Committee.
10J
kg/m2,
-60
-1-1-1-1-1-1—
-30
0
15 30 45 60
90
120
Time (min)
Protocol After an overnight fast each subject was admitted to our Clinical Research Unit where they remained recumbent with an antecubital vein kept patent by slow saline infu¬ sion. A 30-min period was allowed for stabilisation after venipuncture and then, according to a randomized pro¬ tocol, each subject received a. GHRH (1-29) NH2(Serono, Roma, Italy), 100 u.g in 1 ml of saline, iv bolus injection; b. GHRH, 100 (tg iv plus cortisone acetate (Cortone®, Ciba, Switzerland), 25 mg orally, 60 min before GHRH administration; c. GHRH, 100 (tg iv, plus cortisone ace¬ tate, 50 mg orally, 60 min before GHRH administration. Blood samples for GH, cortisol and glucose assays were taken at -60, -30, 0, 15, 30, 45, 60, 90, 120 min from GHRH injection. GH secretory responses were expressed either as absolute values (ug/1) or as peak values (ug/1) or as integrated responses (ug/1) calculated by subtracting mean basal levels from the mean of GH levels at 15, 30, 45, 60, 90, 120 min after GHRH injection. Statistical comparison of the results was made with the Student's i-test. Data with two-sided p
hormone-releasing Andrea Giustina, Mauro
growth hormone response to hormone in normal adult subjects
acetate on
growth
Doga, Corrado Bodini, Angela Girelli, Fabio Legati, Simonetta Bossoni and Giuseppe Romanelli
Cattedra di Patología
Spéciale Medica, University of Brescia, Italy
Abstract Glucocorticoids have been shown
to inhibit GH secretion in normal man when administered in large amounts for several days. The aim of our study was 1. to investigate the acute effects of a single dose of glucocorticoids on GH secretion in normal man; 2. to look at the relationship between the increase in serum cortisol concentration and GH response to the stimuli. Six healthy volunteers received on three occasions in random order an iv injection of GHRH (1-29) NH2, 100 \g=m\g,alone or 60 min after oral administration of either 25 or 50 mg of cortisone acetate. Mean stimulated GH levels, GH peak and integrated GH concentration were significantly lower after GHRH plus cortisone 25 mg than after GHRH alone. Mean GH levels at 15 and 30 min after GHRH injection and the peak GH level showed a further decrease after GHRH plus cortisone 50 mg. We conclude that acute administration of pharmacological doses of glucocorticoids is able to inhibit GH response to GHRH, probably through enhancement of endogenous somatostatin release. Moreover, this pharmacological effect of glucocorticoids seems to be dose-dependent and thus directly related to serum cortisol concentrations.
known to have reduced GH response to these stim¬ uli, and in some patients with acromegaly GH re¬ sponses to GHRH are decreased by pharmacolog¬ ical doses of glucocorticoids (8-9). On the other hand, several studies have reported that glucocorticoids enhance GH release by cul¬ tured rat and human pituitary somatotropes (10), GH gene transcription (11), and GHRH receptor synthesis (12). In adrenalectomized rats the GH response to GHRH has been clearly shown to depend on the presence of physiological glucocorticoid levels (13). Moreover, GH deficiency in pa¬ tients with idiopathic adrenocorticotropin defi¬ ciency resolves during glucocorticoid replacement
(14).
Recently, it has been suggested that the contra¬ dictory evidence from in vitro and in vivo studies regarding the effects of glucocorticoids on GH se¬ cretion could be due to in vivo glucocorticoid en¬ hancement of hypothalamic somatostatin release (15).
Glucocorticoids have long been known to interfere with normal growth, their administration leading to growth retardation in animals (1) as well as in man (2). The role played by glucocorticoids in the regulation of GH secretion is still unclear. Administration of supraphysiological doses of glucocorticoids is able to blunt GH response to var¬ ious pharmacological and physiological stimuli and to diminish GH production rate in normal man (3-7). Moreover, patients with Cushing's disease are
All the cited studies, both those concerning ad¬ ministration of large glucocorticoid doses to normal man and those concerning hypo- or hyperadrenal subjects, did not investigate the relation¬ ship between acute rises in serum cortisol concen¬ trations and pituitary GH responsiveness to the stimuli. Therefore, the aim of our study was 1. to inves¬ tigate the acute effects of a single dose of gluco¬ corticoids on GH secretion in normal man; 2. to look at the relationship between the increase in
serum cortisol concentrations obtained with two different doses of glucocorticoids and the GH re¬ sponse to GHRH administration.
40
30J
Subjects and Methods We studied 6 healthy adult volunteers with no family his¬ tory of endocrine or metabolic disease, all doctors or med¬ ical students, 4 males and 2 females, age range 22-25 with years, body mass index ranging from 18 to 24 normal thyroid and adrenal function. None of the sub¬ jects was taking any drug at the start of the study and all subjects were examined on three different occasions with at least 7-day intervals. The study protocol was approved by the Local Ethical Committee.
10J
kg/m2,
-60
-1-1-1-1-1-1—
-30
0
15 30 45 60
90
120
Time (min)
Protocol After an overnight fast each subject was admitted to our Clinical Research Unit where they remained recumbent with an antecubital vein kept patent by slow saline infu¬ sion. A 30-min period was allowed for stabilisation after venipuncture and then, according to a randomized pro¬ tocol, each subject received a. GHRH (1-29) NH2(Serono, Roma, Italy), 100 u.g in 1 ml of saline, iv bolus injection; b. GHRH, 100 (tg iv plus cortisone acetate (Cortone®, Ciba, Switzerland), 25 mg orally, 60 min before GHRH administration; c. GHRH, 100 (tg iv, plus cortisone ace¬ tate, 50 mg orally, 60 min before GHRH administration. Blood samples for GH, cortisol and glucose assays were taken at -60, -30, 0, 15, 30, 45, 60, 90, 120 min from GHRH injection. GH secretory responses were expressed either as absolute values (ug/1) or as peak values (ug/1) or as integrated responses (ug/1) calculated by subtracting mean basal levels from the mean of GH levels at 15, 30, 45, 60, 90, 120 min after GHRH injection. Statistical comparison of the results was made with the Student's i-test. Data with two-sided p
