capability of the ovary to respond to stimulation by gonadotropic hypophyseal hormone (the thyrotropic hormone). The purpose of the

Transcription

1 612.44: /8 REACTIVITY OF THE THYROID OF THE RABBIT TO THE THYROTROPIC HORMONE OF THE ANTERIOR PIT- UITARY. By K. N. SINHA, Pharacology Departent, King George's Medical College, Lucknow, U.P., India. Fro the Departent of Pharacology, University of Edinburgh. (Received for publication 24th Deceber 1936.) IT is well known that in certain species-e.g. the bitch, the rabbit-the capability of the ovary to respond to stiulation by gonadotropic horone is arkedly reduced after the reoval of the pituitary gland [Reichert et al., 1932; White and Leonard, 1933]. Indeed in the rabbit the reactivity of the ovary is very appreciably reduced three days after the reoval of the hypophysis and later the adinistration of large doses of gonadotropic horone, prepared fro anterior pituitary, or fro pregnancy urine, produces little or no stiulation of the ovary of the hypophysectoied anial [Robson, 1936]. The pituitary produces a nuber of horones which stiulate the growth and the secretory activity of certain other organs. In particular, the activity of the thyroid is known to be under the control of a specific hypophyseal horone (the thyrotropic horone). The purpose of the present investigation was to deterine whether the reactivity of the thyroid of the rabbit to stiulation by thyrotropic horione showed any alteration, siilar to that noted for gonadotropic horone, after reoval of the pituitary. METHOD. The investigations were perfored on eight rabbits. Five anials were hypophysectoied (by the orbital approach; Firor, 1933). The copleteness of the operation was checked by acroscopic exaination of the sella turcica at post-orte exaination. In one anial, pituitary reoval was partial, and about one-third of the gland, in sall but healthy-looking fragents, was found in the pituitary fossa. In the other four anials, post-orte exaination proved that the pituitary reoval had been coplete. Three noral rabbits were used as control. Throughout the whole period of investigation, the anials were kept on a constant diet, naely, 5 g. of cabbage and 2 g. each of oats and bran every evening. Water was given ad lib. throughout. The basal etabolis was first deterined for a nuber

2 332 Sinha of days until a base line was obtained. The anials were then injected with thyrotropic horone for six days, with the exception of the partially hypophysectoied rabbit (T 3) and one copletely hypophysectoied rabbit (T 1) which were injected for seven days, and the basal etabolis was again deterined daily or every second day during the injection period and for soe days after it. Deterination of basal etabolis was ade by the ethod described by Richards and Collison [1928]. The anials reained in the etabolis chaber, therostatically aintained at 25 C., for soe two and a half hours and the readings were taken after the oxygen consuption had attained a steady level. The valves were calibrated for the rate of bubbling every day before the experient. The etabolic rate is expressed in ters of oxygen consuption per inute per hundred square centietres of the body surface, at noral teperature and pressure. All the anials with the exception of two norals were given injections of a preparation of the anterior pituitary lobe, Abinon, for the supply of which I a greatly indebted to Organon Laboratories. The preparation is stated to contain fifty guinea-pig units of thyrotropic horone and five units of gonadotropic horone per c.c. Three rabbits T1, T2, and T3 received -5 c.c. Abinon subcutaneously twice daily (i.e. 5 units per day). Of these, T1 was copletely hypophysectoied, T2 was partially hypophysectoied, and T3 was unoperated. Four rabbits T4, T5, T7, T8 were given intra-uscular injections of the horone-the two hypophysectoied anials T4 and T5 were given -5 c.c. Abinon and the two unoperated T7 and T8 were given 5 units of a purer preparation per day. This latter extract was also received fro Organon Laboratories. RESULTS. The oxygen consuption of the three anials T1, T2, and T3 which received Abinon subcutaneously are given in Table I. and graphically represented in fig. 1. The oxygen consuption of the rabbit Ta6 and others T4, T5, T7, and T8 which received intrauscular injections of the horone are given in Table II. and graphically represented in fig. 2. It will be seen that in all the seven cases the adinistration of thyrotropic horone produced a arked rise in the etabolic rate. An increase in the oxygen consuption becae evident on the fourth day following the first injection in the rabbits injected subcutaneously and a little earlier in those which received intrauscular injections. The axiu oxygen consuption attained by the hypophysectoied rabbits T1, T4, T5, following the adinistration of thyrotropic horone, was 157 c.c., 1-13 c.c., and 1-18 c.c. respectively. The average axiu oxygen consuption works out at 1-29 c.c. The initial average

3 Reactivity of the Thyroid of the Rabbit I! o \T 1 T 7 Days I JO 2 3 FIG '~~~~~~I re\~~~~ C) ~~~/14' FIG. 2.

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6 336 Sinha oxygen consuption of these anials before the adinistration of thyrotropic horone was -78 c.c. If this increase in the etabolic rate is expressed as a percentage of the initial oxygen consuption, the rise aounts to about 65 per cent. of the initial average. The three noral anials T2, T7, T8 show a axiu oxygen consuption of 1x42 c.c., 169 c.c., and 1-42 c.c. respectively. The average of these figures is 1-51 c.c., and this, when copared with the initial average of 1-3 c.c., shows an increase of about 5 per cent. Thus the hypophysectoied anials showed on an average a soewhat greater increase in the etabolis than the unoperated rabbits. Following the rise to the axiu, the oxygen consuption gradually fell. It reached its noral level in five to sixteen days. The three unoperated anials T2, T7, and T8 showed an average oxygen consuption of 1-2 c.c., while the average of the four hypophysectoied rabbits T1, T4, T5, and T6 was -76 c.c. These hypophysectoied rabbits thus showed a lower rate of oxygen consuption as copared with the unoperated anials. The adinistration of thyrotropic horone caused a fall of weight in all the anials. The average fall of weight in the noral rabbits was about 5 per cent. of the initial weight, while it was about 1 per cent. in the case of hypophysectoied anials. The incopletely hypophysectoied rabbit T3 showed an increase of about 35 per cent. in the oxygen consuption and decrease of 7 per cent. in weight. DISCUSSION. It is well known that the thyroid glands of different species of anials show a varying degree of reactivity to the thyrotropic horone of the anterior pituitary, the response of the particular species depending upon its noral activity. In soe species the thyroid gland is norally hyperactive, e.g. in the rat, and in this anial the thyroid is coparatively insensitive to thyrotropic horone stiulation. A dose which will cause a response in a 1 kilograe dog or in a guinea-pig is not adequate to affect the rat [Houssay, 1932]. Collip [1934] indeed has ade the generalisation that the reactivity of the thyroid of an anial varies inversely with the horone content and the horone production of the anial's own gland. There is evidence that after pituitary reoval the thyroid gland of the rat becoes ore sensitive to stiulation by thyrotropic horone. Thus Anderson and Collip [1934] have shown that after hypophysectoy the etabolic rate falls and that the thyroid of the hypophysectoied rat can be stiulated by very sall doses of thyrotropic horone. The present experients have yielded siilar results. Hypophysectoied rabbits showed a lower etabolic rate than the noral anials. Further, the hypophysectoied rabbits showed a soewhat greater increase in

7 Reactivity of the Thyroid of the Rabbit the oxygen consuption, following the adinistration of thyrotropic horone, than the noral rabbits when copared with the initial noral etabolic rate. Hence it can be concluded that reoval of the pituitary in the rabbit has different effects on the reactivity of the organs it controls to the specific hypophyseal stiulating horones. For while the response of the ovary to gonadotropic horone in the hypophysectoied anial is very arkedly reduced, the reactivity of the thyroid to thyrotropic horone is not only not decreased but appears to be soewhat increased. SUMMARY. 1. Adinistration of thyrotropic horone definitely increased the basal etabolic rate of the noral, the partially hypophysectoied, and the copletely hypophysectoied rabbits. 2. The increase in the etabolic rate did not appear before the fourth day of injections in anials receiving subcutaneous injection. The anials receiving intrauscular injection showed an earlier rise in etabolis. 3. Hypophysectoy lowers the etabolic rate. I a very grateful to Professor A. J. Clark, F.R.S., for giving e the opportunity to work in his Departent and to Dr J. M. Robson for doing the operative procedures and giving e advice, help, and guidance throughout. 337 REFERENCES. COLuP, J. (1934). Mount Sinai Hosp. 1, 28. COLuP, J. B., and ANDERSON, E. M. (1934). J. Physiol. 82, 11. FIROR, W. M. (1933). Aer. J. Physiol. 14, 24. HoussAY, B. A. (1932). C.R. Soc. Biol. 111, 459. REICHERT, F. L., PENCHARZ, R. I., SIMPSON, M. E., MEYER, K., and EVANS, H. M. (1932). Aer. J. Physiol. 1, 157. RICHARDS, A. M., and COLLISON, L. W. (1928). J. Physiol. 66, 299. ROBSON, J. M. (1936). Ibid., 75 P. WHITE, W. E., and LEONARD, S. L. (1933). Aer. J. Physiol. 14, 44. VOL. XXVI., NO