The classic postulate by Harris of neuroendocrine control of the anterior pituitary gland predicted that factors would be identified within the hypothalamus that were transported via capillaries of the hypophyseal-portal vessels to regulate pituitary hormone secretion. Two such factors have recently been identified that regulate growth hormone secretion — growth hormone releasing factor (GRF) (1) and the inhibitory peptide, somatostatin (SRIF) (2) (Fig 1). SRIF is widely synthesized and distributed through the hypothalamus and extra-hypothalamic brain (3). Somatostatinergic neurons that originate in perikarya in the periventricular nucleus of the hypothalamus have axons that project via the retrochiasmatic region to terminate in nerve endings in the external layer of the median eminence (4). Manipulation of growth hormone and steroid hormone homeostasis influence preprosomatostatin mRNA (5,6) and SRIF content (7) primarily in this pathway and lesions along the pathway deplete the median eminence of SRIF (8). It thus appears likely that this tract represents the hypophysiotropic somatostatinergic pathway.


Growth Hormone Growth Hormone Secretion Median Eminence Growth Hormone Release Factor Periventricular Nucleus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Rivier J, Spiess J, Thorner M, Vale W. Characterization of a growth hormone releasing factor from a human pancreatic islet tumor, Nature 300:275 (1982).CrossRefGoogle Scholar
  2. 2).
    Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive growth hormone, Science 179:77 (1973).PubMedCrossRefGoogle Scholar
  3. 3).
    Brownstein M, Arimura A, Sato H, Schally AV, Kizer JS. The regional distribution of somatostatin in the rat brain, Endocrinology 96:1456 (1975).PubMedCrossRefGoogle Scholar
  4. 4).
    Epelbaum J, Tapia Arancibia L, Herman JP, Kordon C, Palkovits M. Topography of median eminence somatostatinergic innervation, Brain Research 230:412 (1981).PubMedCrossRefGoogle Scholar
  5. 5).
    Rodgers KV, Vician L, Steiner RA. The effect of hypophysectomy and growth hormone administration on pre-prosomatostatin messenger ribonucleic acid in the periventricular nucleus of the rat hypothalamus. Endocrinology 122:586 (1988).CrossRefGoogle Scholar
  6. 6).
    Werner H, Koch Y, Baldino F, Gozes I. Steroid regulation of somatostatin mRNA in the rat hypothalamus, J Biol Chem 263:7666 (1988).PubMedGoogle Scholar
  7. 7).
    Nakagawa K, Ishizuka T, Obara T, Matsubara M, Akikawa K. Dichotomic action of glucocorticoids on growth hormone secretion Acta Endocrinol (kbh) 116:165 (1987).Google Scholar
  8. 8).
    Critchlow V, Rice RW, Abe K, Vale W. Somatostatin content of the median eminence in female rats with lesion-induced disruption of the inhibitory control of growth hormone secretion, Endocrinology 103:817 (1978).PubMedCrossRefGoogle Scholar
  9. 9).
    Vandepol CJ, Leidy JW, Finger TE, Robbins RJ. Immunohistochemical localization of GRF-containing neurons in rat, Neuroendocrinology 42:143 (1986).PubMedCrossRefGoogle Scholar
  10. 10).
    Plotsky PM, Vale W. Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophyseal-portal circulation of the rat, Science 230:461 (1985).PubMedCrossRefGoogle Scholar
  11. 11).
    Seifert H, Perrin M, Rivier J, Vale W. Growth hormone releasing factor binding sites in rat anterior pituitary membrane homogenates: modulation by glucocorticoids, Endocrinology 117:424 (1985).PubMedCrossRefGoogle Scholar
  12. 12).
    Zysk JR, Cronin MJ, Anderson JM, Thorner MO. Cross-linking of a growth hormone releasing factor-binding protein in anterior pituitary cells, J Biol Chem 261:16781 (1986).PubMedGoogle Scholar
  13. 13).
    Barinaga M, Bilezikijan LN, Vale W, Rosenfeld MG, Evans RM. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription, Nature 314:279 (1985).PubMedCrossRefGoogle Scholar
  14. 14).
    Cronin M, Summers S, Sortino M, Hewlett E. Protein kinase C enhances growth hormone releasing factor (1–40)-stimulated cyclic AMP levels in anterior pituitary, J Biol Chem 261:13932 (1986).PubMedGoogle Scholar
  15. 15).
    Reubi JC, Perrin M, Rivier J, Vale W. High affinity binding sites for somatostatin to rat pituitary, Biochemical and Biophysical Research Communications 105:1538 (1982).PubMedCrossRefGoogle Scholar
  16. 16).
    Koch BD, Dorflinger LJ, Schonbrunn A. Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin, J Biol Chem 260:13138 (1985).PubMedGoogle Scholar
  17. 17).
    Koch BD, Schonbrunn A. Characterization of the cyclic AMP-independent actions of somatostatin in GH cells, J Biol Chem 263:226 (1988).PubMedGoogle Scholar
  18. 18).
    Tannenbaum GS, Martin JB. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat, Endocrinology 98:562 (1976).PubMedCrossRefGoogle Scholar
  19. 19).
    Brook CGD, Hindmarsh PC, Stanhope R. Growth and growth hormone secretion, J Endocr 119:179 (1988).PubMedCrossRefGoogle Scholar
  20. 20).
    Wehrenberg WB, Brazeau P, Luben R, Bohlen P, Guillemin R. Inhibition of pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF), Endocrinology 111:2147 (1982).PubMedCrossRefGoogle Scholar
  21. 21).
    Tannenbaum GS, Ling N. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion, Endocrinology 115:1952 (1984).PubMedCrossRefGoogle Scholar
  22. 22).
    Wood TL, Berelowitz M, McKelvy JF. Regulation of IGF-I and IGF-II mRNAs in the male rat hypothalamus after hypophysectomy, Society for Neuroscience Abstracts Vol 14, part 1:72 (1988).Google Scholar
  23. 23).
    Berelowitz M, Firestone SL, Frohman LA. Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution, Endocrinology 109:714 (1981).PubMedCrossRefGoogle Scholar
  24. 24).
    Berelowitz M, Szabo M, Frohman LA, Firestone SL, Chu L, Hintz RL. Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary, Science 212:1279 (1981).PubMedCrossRefGoogle Scholar
  25. 25).
    Aguila MC, McCann SM. The influence of hGRF, CRF, TRH and LHRH on SRIF release from median eminence fragments, Brain Research 348:180 (1985).PubMedCrossRefGoogle Scholar
  26. 26).
    Martin JB. Neural regulation of growth hormone secretion, New England Journal of Medicine 228:1384 (1973).CrossRefGoogle Scholar
  27. 27).
    Casanueva FF, Villanueva L, Cabranes JA, Cabezas-Cerrato J, Fernandez-Cruz A. Cholinergic mediation of growth hormone secretion induced by arginine, Clonidine and physical exercise in man, J Clin Endocrinol Metab 59:526 (1984).PubMedCrossRefGoogle Scholar
  28. 28).
    Tallo D, Malarkey WB. Adrenergic and dopaminergic modulation of growth hormone and prolactin secretion in normal and tumor bearing human pituitaries in monolayer culture, J Clin Endocrinol Metab 53:1278 (1981).PubMedCrossRefGoogle Scholar
  29. 29).
    Wakabayashi I, Miyazawa Y, Kanda M, Miki N, Demura R, Demura H, Shizume K. Stimulation of immunoreactive somatostatin release from hypothalamic synaptosomes by high K<sup>+</sup> and dopamine, Endocrinol Jpn 24:601 (1977).PubMedCrossRefGoogle Scholar
  30. 30).
    Katajima N, Chihara K, Abe H, Okimura Y, Fujii Y, Sato M, Shakutsui S, Watanabe M, Fujita T. Effects of dopamine on immumoreactive growth hormone — releasing factor and somatostatin secretion from rat hypothalamic slices perifused in vitro, Endocrinology 124:69 (1989).CrossRefGoogle Scholar
  31. 31).
    Aronin N, Coslovsky R, Leeman SE. Substance P and neurotensin: Their roles in the regulation of anterior pituitary function, Annual Review of Physiology 48:537 (1986).CrossRefGoogle Scholar
  32. 32).
    Murphy WA, Lance VA, Heiman ML, Hocart SJ, Coy DH. Prolonged inhibition of growth hormone secretion by peripheral injection of bombesin is mediated by somatostatin in the rat, Endocrinology 117:1179 (1985).PubMedCrossRefGoogle Scholar
  33. 33).
    Katakami H, Kato Y, Matsushita N, Shimatsu A, Imura H. Involvement of hypothalamic somatostatin in glucagon-induced suppression of growth hormone secretion in conscious rats, Peptides 4:849 (1983).PubMedCrossRefGoogle Scholar
  34. 34).
    Rivier C, Vale W. Corticotropin-releasing factor acts centrally to inhibit growth hormone secretion in rat, Endocrinology 114:2409 (1982).CrossRefGoogle Scholar
  35. 35).
    Daughaday WH, Herington AC, Phillips LS. The regulation of growth by endocrines, Annual Review of Physiology 37:211 (1975).PubMedCrossRefGoogle Scholar
  36. 36).
    Lund P, Moats-Staats B, Hynes M, Simmons J, Jansen M, D’Ercole A, Van Wyk J. Somatomedin-C/Insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues, J Biol Chem 261:14539 (1986).PubMedGoogle Scholar
  37. 37).
    Roberts CT, Lasky SR, Lowe WL, Seaman WT, LeRoith D. Molecular cloning of rat insulin-like growth factor I complementary deoxyribounucleic acids: Differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues, Molecular Endocrinology 1:243 (1987).PubMedCrossRefGoogle Scholar
  38. 38).
    Hall K. Effect of intravenous administration of human growth hromone on sulphation factor activity in serum of hypopituitary subjects, Acta Endocrinol (kbh) 66:491 (1971).Google Scholar
  39. 39).
    Phillips LS, Vassilopoulou-Sellin R. Somatomedins, New England Journal of Medicine 302:371–438 (1980).PubMedCrossRefGoogle Scholar
  40. 40).
    Rotwein P, Burgess SK, Milbrandt JD, Krause JE. Differential expression of insulin-like growth factor genes in rat central nervous system, Proc Natl Acad Sci USA 85:265 (1988).PubMedCrossRefGoogle Scholar
  41. 41).
    Adamo M, Werner H, Farnsworth W, Roberts CT, Raizada M, LeRoith D. Dexamethasone reduces steady state insulin-like growth factor I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture, Endocrinology 123:2565 (1988).PubMedCrossRefGoogle Scholar
  42. 42).
    Baskin DG, Wilcox BJ, Figlewicz DP, Dorsa DM. Insulin and insulin-like growth factors in the CNS, Trends in Neurosciences 11:107 (1988).PubMedCrossRefGoogle Scholar
  43. 43).
    Shemer J, Raizada MK, Masters BA, Ota A, Le Roith D. Insulin-like growth factor-I receptors in neuronal and glial cells, J Biol Chem 262:7693 (1987).PubMedGoogle Scholar
  44. 44).
    Adamo M, Werner H, Farnsworth W, Roberts CT, Raizada MK, LeRoith D. Dexamethasone reduces steady state insulin-like growth factor-I messenger ribonucleic acid levels in rat neuronal and glial cells in primary culture, Endocrinology 123:2565 (1988).PubMedCrossRefGoogle Scholar
  45. 45).
    Tannenbaum GS, Guyda HJ, Posner BI. Insulin-like growth factors: A role in growth hormone negative feedback and body weight regulation via brain, Science 220:77 (1983).PubMedCrossRefGoogle Scholar
  46. 46).
    Binoux M, Hossenlopp P, Lassarre C, Hardouin N. Production of Insulin-like growth factors and their carrier by rat pituitary gland and brain expiants in culture, FEBS Letters 124:178 (1981).PubMedCrossRefGoogle Scholar
  47. 47).
    Goodyer CG, deStephano L, Lai WH, Guyda HJ, Posner BI. Characterization of insulin-like growth factor receptors in rat anterior pituitary, hypothalamus, and brain, Endocrinology 114:1187 (1984).PubMedCrossRefGoogle Scholar
  48. 48).
    Rosenfeld RG, Ceda G, Cutler CW, Dollar LA, Hoffman AR. Insulin and Insulin-like growth factor (Somatomedin) receptors on cloned rat pituitary tumor cells, Endocrinology 117:2008 (1985).PubMedCrossRefGoogle Scholar
  49. 49).
    Yamashita S, Melmed S. Insulin-like growth factor I action on rat anterior pituitary cells: Suppression of growth hormone secretion and messenger ribonucleic acid levels, Endocrinology 118:176 (1986).PubMedCrossRefGoogle Scholar
  50. 50).
    Yamashita S, Melmed S. Insulin-like growth factor I regulation of growth hormone gene transcription in primary rat pituitary cells, Journal of Clinical Investigation 79:449 (1987).PubMedCrossRefGoogle Scholar
  51. 51).
    Fagin J, Yamashita S, Melmed S. Ultrashort Feedback Regulation of Pituitary insulin-like growth factor-I mRNA levels by growth hormone, Clinical Research 34:544A (1986).Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Michael Berelowitz
    • 1
  1. 1.Endocrine Div; HSC T15, 060State University of New YorkStony BrookUSA

Personalised recommendations