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Hypothalamic Hormones: Clinical Aspects
Path. Res. Praet. 183, 532-534 (1988)
Hypothalamic Hormones: Clinical Aspects K. Kamijo and A. Yachi Dept. of Internal Medicine, Sapporo Medical College, Sapporo, Japan
SUMMARY
Clinical aspects of TRH, GHRH, Somatostatin (SS) and CRH as well as an effect of glucocorticoid on GH secretion are reported.
I. TRH A paradoxical effect of TRH on GH:
1. Endocrine disorders 2.
3.
4.
5.
CD acromegaly or gigantism @ primary or tertiary hypothyroidism Metabolic disorders CD IDDM" @ severe liver disease @ renal failure Malnutritional state CD anorexia nervosa @ cancer Psychiatric disorders CD depression @ heroin addicts others CD Klinefelter's syndrome @
~-thalassemia
@ fetal life @ Constitutional tall stature .. IDDM: Insulin dependent diabetes mellitus 0344-0338/88/0183-0532$3.50/0
increase in cortisol levels. @ Isolated idiopathic TRH deficiency: Mean age is 30 years, ranged 3 to 63. Until now 3 male and 11 female patients including 2 our cases have been reported. ® Plasma TRH levels: Plasma TRH levels are 9.5 ± 0.9 pg/ml in young males and 10.7 ± 1.5 in females in our RIA. In hyperthyroid patients, mean plasma TRH levels are 9.5 ranged 2.5 to 28.0 and 7.3 ranged 2.5 to 25.6 in hypothyroid patients, not significandy different from normal controls, respectively. II. GHRH GHRH test:
Normal control Acromegaly Cancer
TRH
-+
OGTI L-Dopa CB-154 antidopaminergic agents LHRH
!
f -+ or
f
f f f f
-+
! ! !
-+
-+
f
-+
f f
© 1988 by Gustav Fischer Verlag, Stuttgart
Hypothalamic Hormones: Clinical Aspects' 533 ing tumors. It is also known that sleep induced-GH release is accompanied by an increase in plasma GHRH levels. GHRH concentrations in C5F are low in patients with idiopathic pituitary GH deficiency and undetectable with hypothalamic lesion 4 • Effect of L-dopa on plasma GHRH and GH concentrations are summarized in Table 3. Table 3. Effect of L-Dopa on Plasma GHRH and GH Concentrations GHRH Normal subjects Hypothalamic GH deficiency' Pituitary GH Deficiency" Acromegaly
GH
i
, Chihara et aI., 1986. Mitsuhashi et aI., 1987 and this present. " Shirakawa, 1987. .. Chihara et aI., 1986. U Mitsuhashi et aI., 1987.
III. Somatostatin Three different types of 55-12,55-14 and 55-28 are distributed in the body. It was reported by some authors 6,10 that 55-14 are predominantly distributed in hypothalamus, pancreas, cerebral cortex, retina, whereas 55-28 are rich in intestinal mucosa. Plasma 55 levels are normal in patients with acromegaly12, total pancreatomy and total gasterectomy8. OGTT, arginine, isoproterenol and phentolamine stimulate plasma 5S levels, whereas propranolol suppresses 55 secretions.
IV. Effect of glucocorticoid (GC) on GH secretion It is demonstated in in vitro studies that GC stimulates GH secretion from pituitary gland due to increase in GH gene transcription as well as GH release 2• In vivo condition, GC inhibits GH secretion and its response to various stimuli due to an increase in 55 secretion and a decrease in GHRH secretion from hypothalamus 5 except the stimulative effect by physiological replacement therapy with hydrocortisone in some patients with isolated ACTH deficiency. V.CRH The clinical significance of CRH is summerized in Table 4. Plasma CRH levels have circadian rhythm 9 • Dexamethazone administration suppresses plasma CRH levels, whereas metopirone and insulin hypoglycemia stimulate its release. 5uda et al. 8 reported elevations of CRH in patients with Addison's diseae and Nelson's syndrome and a reduction of CRH in patients with Cushing's disease and syndrome.
Table 4. CRH Test' Basal ACTH levels 1. Adrenal Insufficiency a) Hypothalamic low b) Pituitary low c) Adrenal high 2. Cushing's disease normal or high 3. Cushing's syndrome a) Adrenal tumor undetectable b) Ectopic ACTH syndromehigh c) Nodular hyperplasia 4. Nelson's syndrome
normal low high
5. Anorexia nervosa
normal
ACTH responses to CRH exaggerated absent good hyperresponse absent absent (rarely present) absent markedly increased and prolonged low
, also used in combination with AVP because of synergism between AVP and CRH in their ACTH releasing
Acknowledgements This work was supported by Research Grants from the Foundation of Promotion of Cancer Research.
References 1 Chihara K, Kashio Y, Abe H, Minamitani N, Kaji M, Kito T, Fujita T (1985) Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity levels in cerebrospinal fluid. J Clin Endocrinol Metab 60: 269-278 2 Dobner PR, Kawasaki ES, Yu L-Y, Bancrah FC (1981) Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear predursor in rat pituitary cells. Proc Natl Acad Sci 78: 2230-2234 3 Kameyama K (1986) Secretion of growth hormone-releasing hormone (GHRH) in normal and diseased state. Shikoku Acta Med 42: 26-37 4 Kashio Y, Chihara K, Kaji H, Minamitani N, Kita T, Okimura Y, Abe H, Iwaki J, Fujita T (1985) Presence of growth hormone-releasing factor-like immunoreactivity in human cerebrospinal fluid. J Clin Endocrinol Metab 60: 396-398 5 Nakagawa K, Ishizuka T, Obara T, Matsubara M, Akikawa K (1987) Dichotomic action of glucocorticoid on growth hormone secretion. Acta Endocrinol116: 165-171 6 Patel YC, Wheatly T, Ning C (1981) Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissue and portal plasma of the rat. Endocrinology 109: 1943-1949 7 Shirakawa N (1987) Secretion of growth hormone-releasing factor (GRF) and growth hormone in patients pituitary dwarfism. Shikoku Acta Med 43: 17-27 8 Suda T, Tomori N, Yajima F, Sumitomo T, Nakagawa Y, Ushiyama T, Demura H, Shizume K (1985) Immunoreactive corticotropin-releasing factor in human plasma. J Clin Invest 76: 2026-2029
534 . K. Kamijo and A. Yachi 9 Tanaka K, Watabe T (1987) New aspect of hypothalamic hormones. Folia Endocrinol Jap 3: 31 10 Trent DF, Weir GCl (1981) Heterogenity of somatostatinlike peptides in rat brain, pancreas, and gastrointestinal tract. Endocrinology 108: 2033-2038 11 Tsuda K, Sakurai H, Seino Y, Tanigawa K, Kuzuya H,
Imura H (1981) Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography. Diabetes 30: 471-474 12 Wass JAH, Penman E, Medbak S, Ree lH, Besser GM (1980) CSF and plasma somatostatin levels in acromegaly. Clin Endocrinology 13: 235-241
Received January 30, 1988 . Accepted March 9, 1988
Key words: TRH - GHRH - Somatostatin - CRH - Glu~ocorticoid K. Kamijo, Dept. of Internal Medicine, Sapporo Medical College, Chuo-ku S-l W-16, Sapporo 060, Japan
Hypothalamic Hormones: Clinical Aspects K. Kamijo and A. Yachi Dept. of Internal Medicine, Sapporo Medical College, Sapporo, Japan
SUMMARY
Clinical aspects of TRH, GHRH, Somatostatin (SS) and CRH as well as an effect of glucocorticoid on GH secretion are reported.
I. TRH A paradoxical effect of TRH on GH:
1. Endocrine disorders 2.
3.
4.
5.
CD acromegaly or gigantism @ primary or tertiary hypothyroidism Metabolic disorders CD IDDM" @ severe liver disease @ renal failure Malnutritional state CD anorexia nervosa @ cancer Psychiatric disorders CD depression @ heroin addicts others CD Klinefelter's syndrome @
~-thalassemia
@ fetal life @ Constitutional tall stature .. IDDM: Insulin dependent diabetes mellitus 0344-0338/88/0183-0532$3.50/0
increase in cortisol levels. @ Isolated idiopathic TRH deficiency: Mean age is 30 years, ranged 3 to 63. Until now 3 male and 11 female patients including 2 our cases have been reported. ® Plasma TRH levels: Plasma TRH levels are 9.5 ± 0.9 pg/ml in young males and 10.7 ± 1.5 in females in our RIA. In hyperthyroid patients, mean plasma TRH levels are 9.5 ranged 2.5 to 28.0 and 7.3 ranged 2.5 to 25.6 in hypothyroid patients, not significandy different from normal controls, respectively. II. GHRH GHRH test:
Normal control Acromegaly Cancer
TRH
-+
OGTI L-Dopa CB-154 antidopaminergic agents LHRH
!
f -+ or
f
f f f f
-+
! ! !
-+
-+
f
-+
f f
© 1988 by Gustav Fischer Verlag, Stuttgart
Hypothalamic Hormones: Clinical Aspects' 533 ing tumors. It is also known that sleep induced-GH release is accompanied by an increase in plasma GHRH levels. GHRH concentrations in C5F are low in patients with idiopathic pituitary GH deficiency and undetectable with hypothalamic lesion 4 • Effect of L-dopa on plasma GHRH and GH concentrations are summarized in Table 3. Table 3. Effect of L-Dopa on Plasma GHRH and GH Concentrations GHRH Normal subjects Hypothalamic GH deficiency' Pituitary GH Deficiency" Acromegaly
GH
i
, Chihara et aI., 1986. Mitsuhashi et aI., 1987 and this present. " Shirakawa, 1987. .. Chihara et aI., 1986. U Mitsuhashi et aI., 1987.
III. Somatostatin Three different types of 55-12,55-14 and 55-28 are distributed in the body. It was reported by some authors 6,10 that 55-14 are predominantly distributed in hypothalamus, pancreas, cerebral cortex, retina, whereas 55-28 are rich in intestinal mucosa. Plasma 55 levels are normal in patients with acromegaly12, total pancreatomy and total gasterectomy8. OGTT, arginine, isoproterenol and phentolamine stimulate plasma 5S levels, whereas propranolol suppresses 55 secretions.
IV. Effect of glucocorticoid (GC) on GH secretion It is demonstated in in vitro studies that GC stimulates GH secretion from pituitary gland due to increase in GH gene transcription as well as GH release 2• In vivo condition, GC inhibits GH secretion and its response to various stimuli due to an increase in 55 secretion and a decrease in GHRH secretion from hypothalamus 5 except the stimulative effect by physiological replacement therapy with hydrocortisone in some patients with isolated ACTH deficiency. V.CRH The clinical significance of CRH is summerized in Table 4. Plasma CRH levels have circadian rhythm 9 • Dexamethazone administration suppresses plasma CRH levels, whereas metopirone and insulin hypoglycemia stimulate its release. 5uda et al. 8 reported elevations of CRH in patients with Addison's diseae and Nelson's syndrome and a reduction of CRH in patients with Cushing's disease and syndrome.
Table 4. CRH Test' Basal ACTH levels 1. Adrenal Insufficiency a) Hypothalamic low b) Pituitary low c) Adrenal high 2. Cushing's disease normal or high 3. Cushing's syndrome a) Adrenal tumor undetectable b) Ectopic ACTH syndromehigh c) Nodular hyperplasia 4. Nelson's syndrome
normal low high
5. Anorexia nervosa
normal
ACTH responses to CRH exaggerated absent good hyperresponse absent absent (rarely present) absent markedly increased and prolonged low
, also used in combination with AVP because of synergism between AVP and CRH in their ACTH releasing
Acknowledgements This work was supported by Research Grants from the Foundation of Promotion of Cancer Research.
References 1 Chihara K, Kashio Y, Abe H, Minamitani N, Kaji M, Kito T, Fujita T (1985) Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity levels in cerebrospinal fluid. J Clin Endocrinol Metab 60: 269-278 2 Dobner PR, Kawasaki ES, Yu L-Y, Bancrah FC (1981) Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear predursor in rat pituitary cells. Proc Natl Acad Sci 78: 2230-2234 3 Kameyama K (1986) Secretion of growth hormone-releasing hormone (GHRH) in normal and diseased state. Shikoku Acta Med 42: 26-37 4 Kashio Y, Chihara K, Kaji H, Minamitani N, Kita T, Okimura Y, Abe H, Iwaki J, Fujita T (1985) Presence of growth hormone-releasing factor-like immunoreactivity in human cerebrospinal fluid. J Clin Endocrinol Metab 60: 396-398 5 Nakagawa K, Ishizuka T, Obara T, Matsubara M, Akikawa K (1987) Dichotomic action of glucocorticoid on growth hormone secretion. Acta Endocrinol116: 165-171 6 Patel YC, Wheatly T, Ning C (1981) Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissue and portal plasma of the rat. Endocrinology 109: 1943-1949 7 Shirakawa N (1987) Secretion of growth hormone-releasing factor (GRF) and growth hormone in patients pituitary dwarfism. Shikoku Acta Med 43: 17-27 8 Suda T, Tomori N, Yajima F, Sumitomo T, Nakagawa Y, Ushiyama T, Demura H, Shizume K (1985) Immunoreactive corticotropin-releasing factor in human plasma. J Clin Invest 76: 2026-2029
534 . K. Kamijo and A. Yachi 9 Tanaka K, Watabe T (1987) New aspect of hypothalamic hormones. Folia Endocrinol Jap 3: 31 10 Trent DF, Weir GCl (1981) Heterogenity of somatostatinlike peptides in rat brain, pancreas, and gastrointestinal tract. Endocrinology 108: 2033-2038 11 Tsuda K, Sakurai H, Seino Y, Tanigawa K, Kuzuya H,
Imura H (1981) Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography. Diabetes 30: 471-474 12 Wass JAH, Penman E, Medbak S, Ree lH, Besser GM (1980) CSF and plasma somatostatin levels in acromegaly. Clin Endocrinology 13: 235-241
Received January 30, 1988 . Accepted March 9, 1988
Key words: TRH - GHRH - Somatostatin - CRH - Glu~ocorticoid K. Kamijo, Dept. of Internal Medicine, Sapporo Medical College, Chuo-ku S-l W-16, Sapporo 060, Japan