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. 1986 May;77(5):1704–1711. doi: 10.1172/JCI112490

Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

H Katakami, T R Downs, L A Frohman
PMCID: PMC424578  PMID: 2871046

Abstract

The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and intracellular cyclic AMP accumulation to GRH, while somatostatin (SRIF) suppressive effects on GH secretion were increased. Hypothalamic GRH content was also markedly reduced. T4Rx completely restored hypothalamic GRH content and spontaneous GH secretion despite only partial recovery of pituitary GH content, GRH and SRIF sensitivity, and intracellular cyclic AMP response to GRH. The results indicate multiple effects of hypothyroidism on GH secretion and suggest that a critical role of T4 in maintaining normal GH secretion, in addition to restoring GH synthesis, is related to its effect on hypothalamic GRH.

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Selected References

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  1. Barinaga M., Bilezikjian L. M., Vale W. W., Rosenfeld M. G., Evans R. M. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature. 1985 Mar 21;314(6008):279–281. doi: 10.1038/314279a0. [DOI] [PubMed] [Google Scholar]
  2. Berelowitz M., Firestone S. L., Frohman L. A. Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution. Endocrinology. 1981 Sep;109(3):714–719. doi: 10.1210/endo-109-3-714. [DOI] [PubMed] [Google Scholar]
  3. Berelowitz M., Maeda K., Harris S., Frohman L. A. The effect of alterations in the pituitary-thyroid axis on hypothalamic content and in vitro release of somatostatin-like immunoreactivity. Endocrinology. 1980 Jul;107(1):24–29. doi: 10.1210/endo-107-1-24. [DOI] [PubMed] [Google Scholar]
  4. Bilezikjian L. M., Vale W. W. Stimulation of adenosine 3',5'-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. Endocrinology. 1983 Nov;113(5):1726–1731. doi: 10.1210/endo-113-5-1726. [DOI] [PubMed] [Google Scholar]
  5. Chernausek S. D., Underwood L. E., Utiger R. D., Van Wyk J. J. Growth hormone secretion and plasma somatomedin-C in primary hypothyroidism. Clin Endocrinol (Oxf) 1983 Sep;19(3):337–344. doi: 10.1111/j.1365-2265.1983.tb00007.x. [DOI] [PubMed] [Google Scholar]
  6. Coiro V., Braverman L. E., Christianson D., Fang S. L., Goodman H. M. Effect of hypothyroidism and thyroxine replacement on growth hormone in the rat. Endocrinology. 1979 Sep;105(3):641–646. doi: 10.1210/endo-105-3-641. [DOI] [PubMed] [Google Scholar]
  7. Cronin M. J., Hewlett E. L., Evans W. S., Thorner M. O., Rogol A. D. Human pancreatic tumor growth hormone (GH) - releasing factor and cyclic adenosine 3',5'- monophosphate evoke GH release from anterior pituitary cells: the effects of pertussis toxin, cholera toxin, forskolin, and cycloheximide. Endocrinology. 1984 Mar;114(3):904–913. doi: 10.1210/endo-114-3-904. [DOI] [PubMed] [Google Scholar]
  8. Culler M. D., Kenjo T., Obara N., Arimura A. Stimulation of pituitary cAMP accumulation by human pancreatic GH-releasing factor-(1-44). Am J Physiol. 1984 Nov;247(5 Pt 1):E609–E615. doi: 10.1152/ajpendo.1984.247.5.E609. [DOI] [PubMed] [Google Scholar]
  9. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  10. Dieguez C., Foord S. M., Peters J. R., Hall R., Scanlon M. F. The effects of thyroid hormone deprivation in vivo and in vitro on growth hormone (GH) responses to human pancreatic (tumor) GH-releasing factor (1-40) by dispersed rat anterior pituitary cells. Endocrinology. 1985 Mar;116(3):1066–1070. doi: 10.1210/endo-116-3-1066. [DOI] [PubMed] [Google Scholar]
  11. Frohman L. A., Bernardis L. L. Growth hormone and insulin levels in weanling rats with ventromedial hypothalamic lesions. Endocrinology. 1968 Jun;82(6):1125–1132. doi: 10.1210/endo-82-6-1125. [DOI] [PubMed] [Google Scholar]
  12. Gick G. G., Zeytin F. N., Brazeau P., Ling N. C., Esch F. S., Bancroft C. Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1553–1555. doi: 10.1073/pnas.81.5.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guillemin R., Brazeau P., Böhlen P., Esch F., Ling N., Wehrenberg W. B. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982 Nov 5;218(4572):585–587. doi: 10.1126/science.6812220. [DOI] [PubMed] [Google Scholar]
  14. Harwood J. P., Grewe C., Aguilera G. Actions of growth hormone-releasing factor and somatostatin on adenylate cyclase and growth hormone release in rat anterior pituitary. Mol Cell Endocrinol. 1984 Oct;37(3):277–284. doi: 10.1016/0303-7207(84)90097-2. [DOI] [PubMed] [Google Scholar]
  15. Hervas F., Morreale de Escobar G., Escobar Del Rey F. Rapid effects of single small doses of L-thyroxine and triiodo-L-thyronine on growth hormone, as studied in the rat by radioimmunoassy. Endocrinology. 1975 Jul;97(1):91–101. doi: 10.1210/endo-97-1-91. [DOI] [PubMed] [Google Scholar]
  16. Hinkle P. M., Goh K. B. Regulation of thyrotropin-releasing hormone receptors and responses by L-triiodothyronine in dispersed rat pituitary cell cultures. Endocrinology. 1982 May;110(5):1725–1731. doi: 10.1210/endo-110-5-1725. [DOI] [PubMed] [Google Scholar]
  17. Hinkle P. M., Perrone M. H., Schonbrunn A. Mechanism of thyroid hormone inhibition of thyrotropin-releasing hormone action. Endocrinology. 1981 Jan;108(1):199–205. doi: 10.1210/endo-108-1-199. [DOI] [PubMed] [Google Scholar]
  18. Hymer W. C., Evans W. H., Kraicer J., Mastro A., Davis J., Griswold E. Enrichment of cell types from the rat adenohypophysis by sedimentation at unit gravity. Endocrinology. 1973 Jan;92(1):275–287. doi: 10.1210/endo-92-1-275. [DOI] [PubMed] [Google Scholar]
  19. Iwatsubo H., Omori K., Okada Y., Fukuchi M., Miyai K., Abe H., Kumahara Y. Human growth hormone secretion in primary hypothyroidism before and after treatment. J Clin Endocrinol Metab. 1967 Dec;27(12):1751–1754. doi: 10.1210/jcem-27-12-1751. [DOI] [PubMed] [Google Scholar]
  20. Katakami H., Arimura A., Frohman L. A. Hypothalamic somatostatin mediates the suppression of growth hormone secretion by centrally administered thyrotropin-releasing hormone in conscious rats. Endocrinology. 1985 Sep;117(3):1139–1144. doi: 10.1210/endo-117-3-1139. [DOI] [PubMed] [Google Scholar]
  21. Katakami H., Berelowitz M., Marbach M., Frohman L. A. Modulation of somatostatin binding to rat pituitary membranes by exogenously administered growth hormone. Endocrinology. 1985 Aug;117(2):557–560. doi: 10.1210/endo-117-2-557. [DOI] [PubMed] [Google Scholar]
  22. Katakami H., Kato Y., Matsushita N., Hiroto S., Shimatsu A., Imura H. Involvement of alpha-adrenergic mechanisms in growth hormone release induced by opioid peptides in conscious rats. Neuroendocrinology. 1981 Sep;33(3):129–135. doi: 10.1159/000123216. [DOI] [PubMed] [Google Scholar]
  23. Katakami H., Kato Y., Matsushita N., Shimatsu A., Imura H. Possible involvement of gamma-aminobutyric acid in growth hormone release induced by a Met5-enkephalin analog in conscious rats. Endocrinology. 1981 Oct;109(4):1033–1036. doi: 10.1210/endo-109-4-1033. [DOI] [PubMed] [Google Scholar]
  24. Livesey J. H., Donald R. A. Prevention of adsorption losses during radioimmunoassay of polypeptide hormones: effectiveness of albumins, gelatin, caseins, Tween 20 and plasma. Clin Chim Acta. 1982 Aug 4;123(1-2):193–198. doi: 10.1016/0009-8981(82)90130-9. [DOI] [PubMed] [Google Scholar]
  25. Léan A. D., Ferland L., Drouin J., Kelly P. A., Labrie F. Modulation of pituitary thyrotropin releasing hormone receptor levels by estrogens and thyroid hormones. Endocrinology. 1977 Jun;100(6):1496–1504. doi: 10.1210/endo-100-6-1496. [DOI] [PubMed] [Google Scholar]
  26. MacGillivray M. H., Aceto T., Jr, Frohman L. A. Plasma growth hormone responses and growth retardation of hypothyroidism. Am J Dis Child. 1968 Feb;115(2):273–276. doi: 10.1001/archpedi.1968.02100010275018. [DOI] [PubMed] [Google Scholar]
  27. Peake G. T., Birge C. A., Daughaday W. H. Alterations of radioimmunoassayable growth hormone and prolactin during hypothroidism. Endocrinology. 1973 Feb;92(2):487–493. doi: 10.1210/endo-92-2-487. [DOI] [PubMed] [Google Scholar]
  28. Rivier J., Spiess J., Thorner M., Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982 Nov 18;300(5889):276–278. doi: 10.1038/300276a0. [DOI] [PubMed] [Google Scholar]
  29. Root J. L., Duckett G. E., Sweetland M., Strzelecki J. A., Root A. W. Hypothyroidism blunts the growth hormone (GH) releasing effect of human pancreatic GH releasing factor in the adult male rat in vivo and in vitro. Endocrinology. 1985 May;116(5):1703–1706. doi: 10.1210/endo-116-5-1703. [DOI] [PubMed] [Google Scholar]
  30. SOLOMON J., GREEP R. O. The effect of alterations in thyroid function on the pituitary growth hormone content and acidophil cytology. Endocrinology. 1959 Aug;65(2):158–164. doi: 10.1210/endo-65-2-158. [DOI] [PubMed] [Google Scholar]
  31. Schettini G., Cronin M. J., Hewlett E. L., Thorner M. O., MacLeod R. M. Human pancreatic tumor growth hormone-releasing factor stimulates anterior pituitary adenylate cyclase activity, adenosine 3',5'-monophosphate accumulation, and growth hormone release in a calmodulin-dependent manner. Endocrinology. 1984 Oct;115(4):1308–1314. doi: 10.1210/endo-115-4-1308. [DOI] [PubMed] [Google Scholar]
  32. Srikant C. B., Patel Y. C. Cysteamine-induced depletion of brain somatostatin is associated with up-regulation of cerebrocortical somatostatin receptors. Endocrinology. 1984 Sep;115(3):990–995. doi: 10.1210/endo-115-3-990. [DOI] [PubMed] [Google Scholar]
  33. Szabo M., Chu L., Frohman L. A. Biological effects of an ectopic growth hormone-releasing peptide in cultured adenohypophyseal cells: comparison with growth hormone-releasing activity of porcine hypothalamus. Endocrinology. 1982 Oct;111(4):1235–1240. doi: 10.1210/endo-111-4-1235. [DOI] [PubMed] [Google Scholar]
  34. Szabo M., Frohman L. A. Dissociation of prolactin-releasing activity from thyrotropin-releasing hormone in porcine stalk median eminence. Endocrinology. 1976 Jun;98(6):1451–1459. doi: 10.1210/endo-98-6-1451. [DOI] [PubMed] [Google Scholar]
  35. Takeuchi A., Suzuki M., Tsuchiya S. Effect of thyroidectomy on the secretory profiles of growth hormone, thyrotropin and corticosterone in the rat. Endocrinol Jpn. 1978 Aug;25(4):381–390. doi: 10.1507/endocrj1954.25.381. [DOI] [PubMed] [Google Scholar]
  36. Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
  37. Vale W., Vaughan J., Yamamoto G., Spiess J., Rivier J. Effects of synthetic human pancreatic (tumor) GH releasing factor and somatostatin, triiodothyronine and dexamethasone on GH secretion in vitro. Endocrinology. 1983 Apr;112(4):1553–1555. doi: 10.1210/endo-112-4-1553. [DOI] [PubMed] [Google Scholar]
  38. Veliçelebi G., Santacroce T. M., Harpold M. M. Specific binding of synthetic human pancreatic growth hormone releasing factor (1-40-OH) to bovine anterior pituitaries. Biochem Biophys Res Commun. 1985 Jan 16;126(1):33–39. doi: 10.1016/0006-291x(85)90567-4. [DOI] [PubMed] [Google Scholar]
  39. Wilfinger W. W., Larsen W. J., Downs T. R., Wilbur D. L. An in vitro model for studies of intercellular communication in cultured rat anterior pituitary cells. Tissue Cell. 1984;16(4):483–497. doi: 10.1016/0040-8166(84)90026-0. [DOI] [PubMed] [Google Scholar]
  40. Williams T., Maxon H., Thorner M. O., Frohman L. A. Blunted growth hormone (GH) response to GH-releasing hormone in hypothyroidism resolves in the euthyroid state. J Clin Endocrinol Metab. 1985 Sep;61(3):454–456. doi: 10.1210/jcem-61-3-454. [DOI] [PubMed] [Google Scholar]

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