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THE PITUITARY AND PIGMENTATION
392 NASHsuggests that ephedrine may be effective because of its stimulating and sleep-diminishing effect, and not its local action on the bladder. Belladonna and ephedrine have a modern counterpart in methanthelinium bromide (’Banthine’). This very effective ganglion-blocking agent has been shown to abolish the uninhibited contractions that occur in the bladders of some enuretics. But like many effective remedies, methanthelinium will fall into disrepute if used indiscriminately; in enuresis it should be reserved for cases with uninhibited contractions. Whatever the primary cause or causes of enuresis, the immediate fault is the failure to wake when the bladder empties; and a direct attack may be made at this point. Parents often waken the child shortly before they think the wetting is due to take place ; or an alarm-clock may be used for this purpose. These methods are disappointing. But if the full bladder fails to ring a bell figuratively, the emptying bladder may be made to ring a bell actually and so establish a simple conditioned reflex. This
Conversely
7. Nash, D. F. E.
Lancet, 1950, ii, 485.
Annotations THE
THE PITUITARY AND PIGMENTATION pituitary glands of vertebrates secrete a hormone
variously called melanocyte-stimulating hormone (M.s.H.), melanophore-expanding hormone, and intermedin, whose target organs are the pigment cells-principally those of the skin. In amphibia these pigment cells can quickly darken the skin by expanding black tendrils under the direct influence of M.s.H. In mammals the pigment cells are stimulated by to synthesise more melanin, which darkens the skin more slowly than the mechanism in amphibia. Since the original report by Joresin 1933 several workers have demonstrated this activity in human blood; and in this week’s issue Dr. Hudson and Dr. Bentley show that man, like other animals, has melanocyte-stimulating hormone (they prefer to call it melanophore-expanding hormone) in his pituitary. Lerner and his group at Portland, Oregon,2 injected into volunteers large amounts of a preparation of M.s.H. containing very little corticotrophin or other pituitary hormone. They describe specific, if somewhat cumbersome, methods for urinary and blood assay of the hormone.3 This is important, since biological assay on depends changes in colour in isolated frog’s skin, and various substances, contained in blood and urine, which are not pituitary hormones affect the result. Lerner has defined the normal limits for M.s.H. in blood and urine, and has shown these to be the same for men and women and for albino, white, and coloured people. During pregnancy excretion of M.s.H. increases progressively from the eighth or ninth week until term, after which it reverts to normal in a few days. Excretion of M.S.H. was increased in some patients with Addison’s disease, and in others after bilateral adrenalectomy. Cortisone inhibited heavy excretion of M.s.H. Administration of M.s.H. led to darkening of the skin and formation of new pigmented moles-evidence that the hormone causes multiplication of melanocytes as well as increased melanin synthesis. Some deepening of skin colour was detectable as early as ten hours after high doses. It is now clear that skin darkening produced by commercial preparations of corticotrophin is due to contamination by M.s.H. For some time it was difficult to separate these hormones, and it seemed possible that 1. 2. 3.
Jores, A. Z. ges. exp. Med. 1933, 87, 266. Lerner, A. B., Shizumek, K., Bunding, I. 1954, 14, 1463. Shizume, K., Lerner, A. B. Ibid, p. 1471.
J. clin. Endocrin.
method is perfectly sound, provided that all known factors are also treated and organic disease is excluded. The patient lies on a pad containing an open electrical circuit which is closed immediately the pad is wetted by an electrolytic solution (urine), and this rings a bell. This method, introduced some years ago in the U .8.A., has been tested in this country by DAvIDSoN and DOUGLASS 9 ; and last year BOSTOCK 10 reported from Australia that it had proved successful in 8 out of 12 patients. The method has several disadvantages. The apparatus is expensive, complex, and delicate, and it can be used by only one patient at a time ; the method requires the intelligent cooperation of the child ; and establishing the conditioned reflex may take many weeks. Nevertheless, this method, based on such sound physiological principles, has much to commend it. We are not so well equipped to treat enuresis that we can ignore any promising
technique. 8. Mowrer, O. H. Amer. J. Psychiat. 1938, 51, 163. Mowrer, O. Mowrer, W. M. Amer. J. Orthopsychiat. 1938, 8, 436. 9. Davidson, J. R., Douglass, E. Brit. med. J. 1950, i, 1345. 10. Bostock, J. Med. J. Aust. 1954, ii, 141.
H.,
corticotrophin and M.S.H. were one and the same.4 But M.s.H., unlike corticotrophin, is stable to alkali.5 Complete separation of the activities is difficult, and the purest M.S.H. may possibly have a slight intrinsic corticotrophin-like effect.6 Are these two in fact separated in Nature ? In man, at any rate, they may not be.’ Many states associated with general increase in pigmentation are known to be associated also with increased production of corticotrophin, and adrenal cortical hormones inhibit both corticotrophin and M.S.H.2 There is still no good evidence that M.s.H. causes such pigmentary disturbances as melanomatosis, retinitis pigmentosa, or vitiligo. In man this hormone seems to be a kind of endocrine vestige, of little importance to metabolism and survival but of great interest to phys-
corticotrophin,
icians because it is the inseparable twin of and hence in certain conditions skin pigmentation is a guide to corticotrophin production. Much remains to be learnt. Is there in man a melanocyte-inhibiting hormone analogous to that described for fish by Enami,8 and foreshadowed by the earlier work of Hogben ?9 Does the placenta produce M.s.H., as might be expected if it indeed produces corticotrophin ? 10 At just what stage in melanin synthesis does M.s.H. actWith their methods of assay Dr. Lerner and his colleagues may be able to answer these and other questions. CANCER CLUES
Edgar Allan Poe once wrote of an object being successfully hidden almost literally under the searcher’s nose. Perhaps some vital clues in the cancer mystery may similarly lie under our noses, awaiting discovery an astute observer. There have lately been two reminders of such a possibility-one from Israel and the other from Arizona. Dr. Kalman J. Mann, director of the Hadassah Medical Organisation in Israel, has stated11 that not a single case of lung cancer has been reported among Yemenite Jews in Israel in the last fifteen years. Dr. Mann painted out that these people do not smoke cigarettes but do smoke a narghile-an oriental pipe in which tobacco smoke is drawn through water. An extensive investigation has
by
4. Lancet, 1952, i, 1150. 5. Morris, C. J. O. R. Ibid, p. 1210. 6. Benfey, B. G., Saffran, M., Schally, A. V. Nature, Lond. 1954, 174, 1106. 7. Sulman, F. G. Lancet, 1952, ii, 247. 8. Enami, M. Science, 1955, 121, 36. 9. Hogben, L., Slome, D. Proc. roy. Soc. B. 1931, 108, 10 ; Ibid, 1936, 120, 158. 10. Opsahl, J. C., Long, C. N. H. Yale J. Biol. Med. 1951, 24, 199. 11. New York Times, Feb. 1, 1955.
Conversely
7. Nash, D. F. E.
Lancet, 1950, ii, 485.
Annotations THE
THE PITUITARY AND PIGMENTATION pituitary glands of vertebrates secrete a hormone
variously called melanocyte-stimulating hormone (M.s.H.), melanophore-expanding hormone, and intermedin, whose target organs are the pigment cells-principally those of the skin. In amphibia these pigment cells can quickly darken the skin by expanding black tendrils under the direct influence of M.s.H. In mammals the pigment cells are stimulated by to synthesise more melanin, which darkens the skin more slowly than the mechanism in amphibia. Since the original report by Joresin 1933 several workers have demonstrated this activity in human blood; and in this week’s issue Dr. Hudson and Dr. Bentley show that man, like other animals, has melanocyte-stimulating hormone (they prefer to call it melanophore-expanding hormone) in his pituitary. Lerner and his group at Portland, Oregon,2 injected into volunteers large amounts of a preparation of M.s.H. containing very little corticotrophin or other pituitary hormone. They describe specific, if somewhat cumbersome, methods for urinary and blood assay of the hormone.3 This is important, since biological assay on depends changes in colour in isolated frog’s skin, and various substances, contained in blood and urine, which are not pituitary hormones affect the result. Lerner has defined the normal limits for M.s.H. in blood and urine, and has shown these to be the same for men and women and for albino, white, and coloured people. During pregnancy excretion of M.s.H. increases progressively from the eighth or ninth week until term, after which it reverts to normal in a few days. Excretion of M.S.H. was increased in some patients with Addison’s disease, and in others after bilateral adrenalectomy. Cortisone inhibited heavy excretion of M.s.H. Administration of M.s.H. led to darkening of the skin and formation of new pigmented moles-evidence that the hormone causes multiplication of melanocytes as well as increased melanin synthesis. Some deepening of skin colour was detectable as early as ten hours after high doses. It is now clear that skin darkening produced by commercial preparations of corticotrophin is due to contamination by M.s.H. For some time it was difficult to separate these hormones, and it seemed possible that 1. 2. 3.
Jores, A. Z. ges. exp. Med. 1933, 87, 266. Lerner, A. B., Shizumek, K., Bunding, I. 1954, 14, 1463. Shizume, K., Lerner, A. B. Ibid, p. 1471.
J. clin. Endocrin.
method is perfectly sound, provided that all known factors are also treated and organic disease is excluded. The patient lies on a pad containing an open electrical circuit which is closed immediately the pad is wetted by an electrolytic solution (urine), and this rings a bell. This method, introduced some years ago in the U .8.A., has been tested in this country by DAvIDSoN and DOUGLASS 9 ; and last year BOSTOCK 10 reported from Australia that it had proved successful in 8 out of 12 patients. The method has several disadvantages. The apparatus is expensive, complex, and delicate, and it can be used by only one patient at a time ; the method requires the intelligent cooperation of the child ; and establishing the conditioned reflex may take many weeks. Nevertheless, this method, based on such sound physiological principles, has much to commend it. We are not so well equipped to treat enuresis that we can ignore any promising
technique. 8. Mowrer, O. H. Amer. J. Psychiat. 1938, 51, 163. Mowrer, O. Mowrer, W. M. Amer. J. Orthopsychiat. 1938, 8, 436. 9. Davidson, J. R., Douglass, E. Brit. med. J. 1950, i, 1345. 10. Bostock, J. Med. J. Aust. 1954, ii, 141.
H.,
corticotrophin and M.S.H. were one and the same.4 But M.s.H., unlike corticotrophin, is stable to alkali.5 Complete separation of the activities is difficult, and the purest M.S.H. may possibly have a slight intrinsic corticotrophin-like effect.6 Are these two in fact separated in Nature ? In man, at any rate, they may not be.’ Many states associated with general increase in pigmentation are known to be associated also with increased production of corticotrophin, and adrenal cortical hormones inhibit both corticotrophin and M.S.H.2 There is still no good evidence that M.s.H. causes such pigmentary disturbances as melanomatosis, retinitis pigmentosa, or vitiligo. In man this hormone seems to be a kind of endocrine vestige, of little importance to metabolism and survival but of great interest to phys-
corticotrophin,
icians because it is the inseparable twin of and hence in certain conditions skin pigmentation is a guide to corticotrophin production. Much remains to be learnt. Is there in man a melanocyte-inhibiting hormone analogous to that described for fish by Enami,8 and foreshadowed by the earlier work of Hogben ?9 Does the placenta produce M.s.H., as might be expected if it indeed produces corticotrophin ? 10 At just what stage in melanin synthesis does M.s.H. actWith their methods of assay Dr. Lerner and his colleagues may be able to answer these and other questions. CANCER CLUES
Edgar Allan Poe once wrote of an object being successfully hidden almost literally under the searcher’s nose. Perhaps some vital clues in the cancer mystery may similarly lie under our noses, awaiting discovery an astute observer. There have lately been two reminders of such a possibility-one from Israel and the other from Arizona. Dr. Kalman J. Mann, director of the Hadassah Medical Organisation in Israel, has stated11 that not a single case of lung cancer has been reported among Yemenite Jews in Israel in the last fifteen years. Dr. Mann painted out that these people do not smoke cigarettes but do smoke a narghile-an oriental pipe in which tobacco smoke is drawn through water. An extensive investigation has
by
4. Lancet, 1952, i, 1150. 5. Morris, C. J. O. R. Ibid, p. 1210. 6. Benfey, B. G., Saffran, M., Schally, A. V. Nature, Lond. 1954, 174, 1106. 7. Sulman, F. G. Lancet, 1952, ii, 247. 8. Enami, M. Science, 1955, 121, 36. 9. Hogben, L., Slome, D. Proc. roy. Soc. B. 1931, 108, 10 ; Ibid, 1936, 120, 158. 10. Opsahl, J. C., Long, C. N. H. Yale J. Biol. Med. 1951, 24, 199. 11. New York Times, Feb. 1, 1955.