Role of Trophic Hormones in Regulation of Growth and Function of Responsive Cells

  • A. Jagannadha Rao
  • J. A. Long
  • B. D. Gondos
  • J. G. Lehoux
  • J. Ramachandran
Part of the Biochemical Endocrinology book series (BIOEND, volume 1)


The role of the trophic hormones, Adrenocorticotropic hormone (ACTH) and Luteinizing hormone (LH) in regulating growth and function of adrenocortical cells and Leydig cells respectively, has been investigated using an immunological approach. Antisera to porcine ACTH and ovine LH were raised in rabbits and characterized for specificity, ability to neutralize rat ACTH and LH respectively. Administration of ACTH antiserum to rats for 6 to 10 days did not cause any decrease in the weight of the adrenals, but resulted in a significant decrease in serum corticosterone. Also when the adrenocortical cells isolated from normal rabbit serum (NRS) or ACTH antiserum treated rats were examined for their ability to respond to exogenous ACTH, there was a drastic decrease in the response of the latter as judged by corticosterone production. It is known that in an unilaterally adrenalectomized rat there is compensatory hypertrophy of the remaining adrenal and this growth has been shown to be due to actual increase in cell number. Administration of ACTH antiserum to unilaterally adrenalectomized rats did not in any way prevent the compensatory hypertrophy response of the remaining adrenal as judged by weight, DNA, protein or yield of adrenocortical cells.


Luteinizing Hormone Leydig Cell Normal Rabbit Serum Adrenocortical Cell Adrenal Weight 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aguilera, G., Menard, R. H., and Catt, K. J., 1980a, Regulatory actions of angiotensin II on receptors and steroidogenic enzymes in adrenal glomerulosa cells, Endocrinology 107:55.PubMedCrossRefGoogle Scholar
  2. Aguilera, G., Schirar, A., Baukal, A., Catt, K. J., 1980b, Angiotensin II receptors: Properties and regulation in adrenal glomerulosa cells, Circ. Res. Suppl. 46:118.Google Scholar
  3. Aguilera, G., Fujita, K., and Catt, K. J., 1981, Mechanism of inhibition of aldosterone secretion by adrenocorticotrophin, Endocrinology 108:522.PubMedCrossRefGoogle Scholar
  4. Astwood, E. B., 1955, Growth hormone and adrenocorticotrophin, in: “The Hormones” Volume 3, p. 235, G. Pincus and K. V. Thimann, eds., Academic Press, New York.Google Scholar
  5. Bascom, K. F., and Osterud, H. L., 1925, Quantitative studies of the testicle. II Pattern and total tubule length in the testicles of certain mammals, Anat. Rec. 31:159.CrossRefGoogle Scholar
  6. Baumann, K., and Muller, 1974, Effects of hypophysectomy with or without ACTH maintenance therapy on the final steps of aldosterone biosynthesis in the rat, Acta Endocrinol. (kbh) 76:102.Google Scholar
  7. Blairwest, J. R., Coghlan, J. P., Denton, D. A., Goding, J. R., Wintour, M., and Wright, R. D., 1963, The control of aldosterone secretion, Rec. Prog. Horm. Res. 19:311.Google Scholar
  8. Bourdel, G., and Li, C. H., 1963, Effect of rabbit antiserum to sheep pituitary interstitial stimulating hormone in adult female rats, Acta Endocrinol.(kbh) 42:473.Google Scholar
  9. Bransome, E. D., and Reddy, W. J., 1961, Studies of adrenal nuclei acids: The influence of ACTH, unilateral adrenalectomy and growth hormone upon adrenal RNA and DNA in the dog, Endocrinology 69:997.PubMedCrossRefGoogle Scholar
  10. Carr, I., 1959, The human adrenal gland at the time of death, J. Path. Bacteriol. 78:533.CrossRefGoogle Scholar
  11. Cater, D. B., and Stack-Dunne, M. P., 1953, Histological changes in the adrenal of the hypophysectomized rat after treatment with pituitary preparations, J. Path. Bacteriol. 66:119.CrossRefGoogle Scholar
  12. Cater, D. B., and Stack-Dunne, M. P., 1955, The effects of growth hormone and corticotrophin upon the adrenal weight and adrenocortical mitotic activity, J. Endocrinol. 12:174.PubMedCrossRefGoogle Scholar
  13. Christensen, A. K., 1975, Leydig cells in: “Handbook of Physiology”, Section 7, Volume 5, p. 57, R. O. Greep, E. B. Astwood, eds., Williams and Wilkins, Baltimore, MD.Google Scholar
  14. Christensen, A., and Peacock, K., 1980, Increase in leydig cell number in testes of adult rats treated chronically with an excess of human chorionic gonadotrophin, Biol. Reprod. 22:383.PubMedGoogle Scholar
  15. Cooke, B. A., Manszen, F. H. A., Clotscher, W. F., and Van Der Molen, H. J., 1975, Effect of protein synthesis inhibitors on testosterone production in rat testes interstitial tissue and leydig cell preparations, Biochem. J. 150:413.PubMedGoogle Scholar
  16. Contopoulous, A. N., and Hayashida, T., 1963, Neutralization of activity of circulating gonadotrophic hormones by antiserum to rat pituitary, J. Endocrinol. 25:451.CrossRefGoogle Scholar
  17. Dallman, M. F., Engeland, W. C., Schinsako, J., 1976, Compensatory adrenal growth: a neorally mediated reflex, Am. J. Physiol. 231:408.PubMedGoogle Scholar
  18. Dallman, M. F., Engeland, W. C., McBride, M. H., 1977, The neural regulation of compensatory hypertrophy, Ann. New York Acad. Sci. 297:373.CrossRefGoogle Scholar
  19. Dallman, M. F., Engeland, W. C., Holzwarth, M. A., Scholz, P. M., 1980, Adrenocorticotropin inhibits compensatory adrenal growth after unilateral adrenalectomy, Endocrinology 107:1397.PubMedCrossRefGoogle Scholar
  20. Davis, J. O., 1975, Regulation of aldosterone secretion in: “Handbook of Physiology”, Section 7, Volume 4, p. 77, R. 0. Greep and E. B. Astwood, eds., Williams and Wilkins, Baltimore, MD.Google Scholar
  21. Dixon, H. B. F., Stack-Dunne, M. P., Young, F. G., and Carter, D. B., 1951, Influence of adrenotrophic hormone fractions on adrenal repair and on adrenal ascorbic acid, Nature168:1084.PubMedCrossRefGoogle Scholar
  22. Douglas, J., Catt, 1976, Regulation of Angiotensin II receptors in rat adrenal cortex by dietary electrolytes, J. Clin. Invest. 58:834.PubMedCrossRefGoogle Scholar
  23. Douglas, J., Aguilera, G., Kondo, T., Catt, K. J., 1978, Angiotensin II receptors and aldosterone production in rat adrenal glomerulosa cells, Endocrinology102:685.PubMedCrossRefGoogle Scholar
  24. Dym, M., Madhwaraj, H. G., and Chemes, H. E., 1977, Response of the testes to selective withdrawl of LH or FSH using antigonadotropic sera in: “The Testes in Normal and Infertile Man”, p. 97, P. Troen and H. R. Nankin, ed., Raven Press, New York.Google Scholar
  25. Eik-Nes, K. B., 1970, Synthesis and secretion of andostenedione and testosterone, in: “The Androgens of the Testis”, p. 1, K. B. Eik-Nes, ed., Marrel and Dekker, New York.Google Scholar
  26. Farese, R. V., and Reddy, W. J., 1963, Observations on the interactions between adrenal protein RNA and DNA during prolonged ACTH administration, Biochem. Biophys. Acta76:145.CrossRefGoogle Scholar
  27. Fredlund, P., Saltman, S., and Catt, K. J., 1975, Aldosterone production by isolated adrenal glomerulosa cells: stimulation by physiological concentrations of Angiotensin II, Endocrinology 97:1577.PubMedCrossRefGoogle Scholar
  28. Garren, L. D., 1968, The mechanism of action of adrenocorticotropic hormone, Vit and Horm. 26:119.CrossRefGoogle Scholar
  29. Garren, L. D., Gill, G. N., Masui, H., and Walton, G. M., 1971, On the mechanism of action of ACTH, Rec. Prog. Horm. Res. 27:433.PubMedGoogle Scholar
  30. Gill, G. N., 1972, Mechanism of ACTH action, Metabolism, 21:571.PubMedCrossRefGoogle Scholar
  31. Gill, G. N., III, C. R., Simonian, M. H., 1977, Angiotensin stimulation of bovine adrenocortical cell, Proc. Natl. Acad. Sci. USA 74:5569.PubMedCrossRefGoogle Scholar
  32. Glossmann, H., Baukal, A., and Catt, K. J., 1974, Properties of angiotensin receptors in the bovine and rat adrenal cortex, J. Biol. Chem. 249:825.PubMedGoogle Scholar
  33. Gondos, B., Jagannadha Rao, A., and Ramachandran, J., 1980, Effects of antiserum to luteinizing hormone on the structure and function of rat leydig cells, J. Endocrinol. 87:265.PubMedCrossRefGoogle Scholar
  34. Gospadorowicz, D., Jones, K., Sato, G., 1974, Purification of a growth factor for ovarian cells from bovine pituitary gland, Proc. Natl. Acad. Sci. USA 71:2295.CrossRefGoogle Scholar
  35. Gospadorowicz, D., and Handley, H. H., 1975, Stimulation of division of Y-l adrenal cells by a growth factor isolated from bovine pituitary glands, Endocrinology 97:102.CrossRefGoogle Scholar
  36. Greep, R. O., 1974, History of research on anterior typophysical hormones, in: “Handbook of Physiology”, Section 7, Volume 4, p. 1, R. O. Greep, E. B. Astwood, eds., Williams and Wilkins, Baltimore, MD.Google Scholar
  37. Hall, P. F., 1970, Gonadotrophic regulation of testicular function, in: “The Androgens of the Testis”, p. 73, K. B. Eik-Nes, ed., Mercel Dekker Inc., New York.Google Scholar
  38. Haning, R., Tait, S. A., and Tait, J. F., 1970, In vitro effects of ACTH, Angiotensin, Serotonin and Potassium on steroid output and conversion of corticosterone to aldosterone by isolated adrenal cells, Endocrinology 87:1147.PubMedCrossRefGoogle Scholar
  39. Hornsby, P. J., O’Hare, M. J., and Neville, A. M., 1973, Effect of ACTH on biosynthesis of aldosterone and corticosterone by monolayer culture of rat adrenal zona glomerulosa cells, Biochem. Biophys. Res. Comm. 54:1554.PubMedCrossRefGoogle Scholar
  40. Hornsby, P. J., O’Hare, M. J., and Neville, A. M., 1974, Functional and morphological observations on rat adrenal zona glomerulosa cells in monolayer culture, Endocrinology95:1240.PubMedCrossRefGoogle Scholar
  41. Huhtaniemi, I. T., Mohan, K., and Catt, K. J., 1981, Regulation of LH receptors and steroidogenesis in the neonatal rat testes, Endocrinology 109:588.PubMedCrossRefGoogle Scholar
  42. Hansson, V., Ritzen, M., Purvis, K., French, F. S., 1978, Endocrine approaches to male contraception, Scriptor, Copenhagen.Google Scholar
  43. Idleman, S., 1970, Ultrastructure of the mammalian adrenal cortex, Int. Rev. Cytol. 27:181.CrossRefGoogle Scholar
  44. Imrie, R. C., Ramaiah, T. R., Antoni, F., Hutchinson, W. C., 1965, The effect of ACTH on the nuclei acid metabolism of the rat adrenal gland, J. Endocrinol. 32:302.CrossRefGoogle Scholar
  45. Ingle, D. J., 1951, The functional interrelationship of the anterior pituitary and adrenal cortex, Ann. Inter. Med. 35:652.Google Scholar
  46. Jagannadha Rao, A., Madhwa Raj, H. G., and Moudgal, N. R., 1972, Effect of LH, FSH and their antisera on gestation in the hamster, (Mesocricetus auratus), J. Reprod. Fert. 29:239.CrossRefGoogle Scholar
  47. Jagannadha Rao, A., Moudgal, N. R., Madhwa Raj, H. G., Lipner, H., Greep, R. P., 1974, The role of FSH and LH in the initiation of ovulation in rats and hamsters; a study using rabbit antisera to ovine FSH and LH, J. Reprod. Fert. 37:323.CrossRefGoogle Scholar
  48. Jagannadha Rao, A., Long, J. A., and Ramachandran, J., 1978, Effects of antiserum to adrenocorticotropin on adrenal growth and function, Endocrinology 102:371.PubMedCrossRefGoogle Scholar
  49. Jagannadha Rao, A., and Lehoux, J. G., 1979, Effect of ACTH on 125I labelled angiotensin II binding and response by rat adrenal glomerulosa cells, FEBS Letters 105:325.PubMedCrossRefGoogle Scholar
  50. Jagannadha Rao, A., Behrens, C., and Ramachandran, J., 1980, Immunochemical studies of adrenocorticotropin using tritium labelled hormone, Int. J. Peptide Protein Res. 15:480.CrossRefGoogle Scholar
  51. Jagannadha Rao, A., 1982, Effect of rabbit antiserum to ovine LH on reproductive organs in male hamsters and guinea pigs, Experientia, 38:279.PubMedCrossRefGoogle Scholar
  52. Jailer, J. W., Longson, D., Christy, N. D., 1957, Cushing’s Syndrome II. Adrenal weight maintaining activity in the plasma of patients with cushing’s syndrome, J. Clin. Endocrinol. Metab. 36:1608.Google Scholar
  53. Janszen, F. H. A., Cooke, B. A., Van Der Molen, H. J., 1977, Specific protein synthesis in isolated rat leydig cells, Biochem. J. 162:341.PubMedGoogle Scholar
  54. Kahri, A. J., 1966, Histochemical and electron microscopic studies on the cells of rat adrenal cortex in tissue culture, Acta Endocrinol. 52: Suppl. (108) 1.PubMedGoogle Scholar
  55. Kahri, A. I., Huhtaniemi, I., and Salmenpera, M., 1976, Steroid formation and differentiation of cortical cells in tissue culture of human foetal adrenals in the presence and absence of ACTH, Endocrinology 98:33.PubMedCrossRefGoogle Scholar
  56. Kimura, T., 1969, Effect of hypophysectomy and ACTH administration on the level of adrenal cholesterol side chain desmolase, Endocrinology 85:492.PubMedCrossRefGoogle Scholar
  57. Kowi, J., 1970, ACTH and the metabolism of adrenal cell cultures. Rec. Prog. Horm. Res. 26:623.Google Scholar
  58. Kortiz, S. B., Girija, B., and Schwartz, E., 1977, ACTH action on adrenal steroidogenesis, Ann. New York Acad. Sci. 297:329.CrossRefGoogle Scholar
  59. Liddle, G. W., Island, D., Rinfret, A. P., Forsham, P. H., 1954, Factors enhancing the response of the human adrenal to corticotropin. Is there an adrenal growth factor? J. Clin. Endocrinol. Metab. 14:839.PubMedCrossRefGoogle Scholar
  60. Liles, S., and Ramachandran, J., 1977, Regulation of 5–3β hydroxysteroid dehydrogenase isomerase activity in adrenocortical cell cultures by ACTH, Biochem. Biophys. Res. Comm. 79:226.PubMedCrossRefGoogle Scholar
  61. Long, J. A., 1975, Zonation of the mammalian adrenal cortex, in: “Handbook of Physiology”, Section 7, Volume 6, p. 13, R. R. O. Greep and E. B. Astwood, eds., Williams and Wilkins, Baltimore, MD.Google Scholar
  62. Lostroh, A. J., and Li, C. H., 1957, Stimulation of the sex accessories of hypophysectomized male rats by non-gonadotropic hromones of the pituitary gland, Acta Endocrinol. 25:1.PubMedGoogle Scholar
  63. Madhwa Raj, H. G., and Moudgal, N. R., 1970, Hormonal control of gestation in the rat, Endocrinology 86:874.PubMedCrossRefGoogle Scholar
  64. Malamed, S., 1975, Ultrastructure of the mammalian adrenal cortex in relation to secretory of function in: “Handbook of Physiology”, Section 7, Volume 6, p. 25, R. O. Greep and E. B. Estwood, eds., Williams and Wilkins, Baltimore.Google Scholar
  65. Manuelidis, L., and Mulrow, D., 1974, Aldosterone production by adrenal cultures via dibCAMP and the reversibility of ACTH and dibCAMP induced changes, Endocrinology 95:728.PubMedCrossRefGoogle Scholar
  66. Masui, H., and Garren, L. D., 1970, The mechanism of action of adrenocorticotrophic hormone stimulation of DNA polymerase and thymidine kinase activity in adrenal glands, J. Biol. Chem. 245:2627.PubMedGoogle Scholar
  67. Masui, H., and Garren, L. D., 1971, Inhibition of replication in functional mouse adrenal tumor cells by adrenocorticotrophic hormone mediated by adrenosine 3’5’ cycle monophosphate, Proc. Natl. Acad. Sci. USA 68:3206.PubMedCrossRefGoogle Scholar
  68. Means, A. R., Dedman, M. R., Tash, J. S., Tindal, D. J., Vansickle, M., Walsh, M. J., 1980, Regulation of the testes sertoli cell by follicle stimulating hormone, Ann. Rev. Physiol. 42:59.CrossRefGoogle Scholar
  69. Moudgal, N. R., Jagannadha Rao, A., Maneckjee, R., Murlidhar, K., Venkatramiah, M., Sheela Rani, C. S., 1974, Gonadotropins and their antibodies, Rec. Prog. Horm. Res. 30:47.PubMedGoogle Scholar
  70. Muller, A. F., Riondel, A. M., Manning, E. L., 1956, Effect of corticotrophin on secretion of aldosterone, Lancet 2:1021.CrossRefGoogle Scholar
  71. Muller, J., 1970, Decreased aldosterone production by rat adrenal tissue in vitro due to treatment with 9α flurocortisol dexamethasone and adrenocorticotrophin in vivo, Acta Endocrinol. (kbh) 63:1.Google Scholar
  72. Muller, J., 1978, Suppression of aldosterone biosynthesis by treatment of rats with adrenocorticotrophin: Comparison with glucocorticoid effects, Endocrinology 103:2061.PubMedCrossRefGoogle Scholar
  73. Nieschlag, E., (ed.), 1975, Immunization with hormones in reproduction research, North Holland, Amsterdam.Google Scholar
  74. Nussdorfer, G. G., Mazzocchi, G., Robba, C., Belloni, A. S., Rebuftat, D., 1977, Effects of ACTH and dexamethasone on the zona glomerulosa of the rat adrenal cortex: an ultrastructural sterological study, Acta. Endocrinol. (kbh) 85:608.Google Scholar
  75. O’Hare, M. J., and Neville, A. M., 1973, Morphological responses to corticotropin and cyclin AMP by adult rat adrenocortical cells in monolayer culture, J. Endocrinol. 56:529.PubMedCrossRefGoogle Scholar
  76. Payet, N., Isler, H., 1976, Adrenal Glomerulosa mitotic stimulation by posterior pituitary hormones, Cell Tiss. Res. 172:93.CrossRefGoogle Scholar
  77. Payne, A. H., Downing, J. R., and Wong, K. L., 1980, LH receptors and testosterone synthesis in two distinct populations of Leydig cells, Endocrinology 106:1424.PubMedCrossRefGoogle Scholar
  78. Peytremann, A., Nicholson, W. E., Brown, R. D., Liddle, G. W., and Hardman, J. G., 1973, Comparative effects of angiotensin and ACTH on cyclic AMP and steroidogenesis in isolated bovine adrenal cells, J. Clin. Invest. 52:835.PubMedCrossRefGoogle Scholar
  79. Purvis, J. L., Canick, J. A., Mason, J. I., Estabrook, R. W., and McCarthy, J. L., 1973, Lifetime of adrenal cytochrome P-450 as influenced by ACTH, Ann. New York Acad. Sci. 212:319.CrossRefGoogle Scholar
  80. Purvis, K., Clausen, O. P. F., and Hansson, V., 1978, Functional characteristics of rat Leydig cells, Ann. Biol. Anim. Biochem. Biophys. 18:595.CrossRefGoogle Scholar
  81. Purvis, K., Cusan, L., and Hansson, V., 1981, Regulation of steroidogenesis and steroid action in Leydig cells, J. Steroid Biochem. 15:77.PubMedCrossRefGoogle Scholar
  82. Purvis, K., Clausen, O. P. F., and Hansson, V., 1980, Effects of age and hypophysectomy on responsiveness of rat Leydig cells to LH/hCG, J. Reprod. Fertil. 60:77.PubMedCrossRefGoogle Scholar
  83. Quadri, S. K., and Spies, H. G., 1966, Inhibition of spermatogenesis and ovulation in rabbits with antiovine LH rabbit serum, Proc. Soc. Expt. Biol. Med. 123:809.Google Scholar
  84. Ramachandran, J., and Suyama, A. T., 1975, Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin, Proc. Natl. Acad. Sci. USA 72:113.PubMedCrossRefGoogle Scholar
  85. Ramachandran, J., Jagannadha Rao, A., and Liles, S., 1977, Studies on the trophic action of ACTH, Ann. New York Acad. Sci. 297:336.CrossRefGoogle Scholar
  86. Rybak, S. M., and Ramachandran, J., 1982, Mechanism of induction of 5–3β-Hydroxysteroid dehydrognease-isomerse activity in rat adrenocortical cells by corticotropin, Endocrinology111:427.PubMedCrossRefGoogle Scholar
  87. Sairam, M. R., Jagannadha Rao, A., and Li, C. H., 1974, Termination of pregnancy in the rat by the antiserum to β subunit of ovine interstitial cell stimulating hormone, Proc. Soc. Expt. Biol. Med. 147:823.Google Scholar
  88. Sairam, M. R., Jagannadha Rao, A., and Li, C. H., 1975, The use of antiserum to rat prolactin to evaluate its role as luteotropin in the hamster, Acta Endocrinol. 79:351.PubMedGoogle Scholar
  89. Suyama, A. T., Long, J. A., and Ramachandran, J., 1977, Ultrastructural changes induced by ACTH in normal adrenocortical cells in culture, J. Cell Biol. 72:757.PubMedCrossRefGoogle Scholar
  90. Schafer, G., Helstein, A. F., Hilz, H., 1982, Steroidogenic capacity of isolated mouse Leydig cells does not decrease with age, Endocrinology 110:1362.PubMedCrossRefGoogle Scholar
  91. Smith, P. E., 1927, The disabilities caused by hypophysectomy and their repair, J. Ann. Med. Assoc. 88:158.CrossRefGoogle Scholar
  92. Smith, P. E., 1930, Hypophysectomy and replacement therapy in the rat, Ann. J. Anat. 45:205.Google Scholar
  93. Steinberger, E., and Steinberger, A., 1972, The testis: Growth vs. function in: “Regulation of Organ and Tissue Growth” p. 299, R. G. Goss, ed., Academic Press, New York.Google Scholar
  94. Tepperman, J., Engel, F. L., Long, C. N. H., 1943, A review of adrenal cortical hypertrophy, Endocrinology 32:373.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • A. Jagannadha Rao
    • 1
  • J. A. Long
    • 2
  • B. D. Gondos
    • 3
  • J. G. Lehoux
    • 4
  • J. Ramachandran
    • 5
  1. 1.Department of BiochemistryIndian Institute of ScienceBangaloreIndia
  2. 2.Department of AnatomyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of PathologyUniversity of Conneticuit Health CentreFarmingtonUSA
  4. 4.Faculty of MedicineUniversity of SherbrookeSherbrookeCanada
  5. 5.Hormone Research LaboratoryUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations