Sex difference in adaptation of serum calcium level to the gradual deprivation of parathyroid hormone and to the following thyroidectomy.

The time course of adaptation of the serum calcium level to the gradual deprivation of parathyroid hormone was studied in adult male and female rats. In addition, the role of thyrocalcitonin and thyroid hormones in adaptive changes in serum calcium was assessed in the surgically parathyroidectomized animals. Simultaneous bilateral parathyroidectomy, thyroparathyroidectomy or the second unilateral parathyroidectomy performed72hr after the first unilateral parathyroidectomy produced a prompt fall in serum calcium level leading to the lowest value at10hr and the significantly lower calcium level retained for one week-observation. Unilateral parathyroidectomy resulted in a transient fall in the serum calcium level and to a rapid return to the subnormal range in24hr in both sexes. When the second unilateral parathyroidectomy was carried out1or6weeks after the first unilateral parathyroidectomy, the serum calcium in female rats showed a slight decrease until10hr and returned to the normal level in one week, but in male rats no further decline or a gradual decrease was seen. Bilateral thyroidectomy performed10weeks after the second unilateral parathyroidectomy resulted in a gradual increase in the serum calcium above the normal range in female rats. In male rats, the serum calcium level tended to drop until10hr and returned to the initial level or to the normal range. Bilateral thyroidectomy performed one week after simultaneous bilateral parathyroidectomy led to a further decline in serum calcium in both male and female rats. The results indicate that adaptation of the serum calcium level toward the normal range occurs in the absence of parathyroid hormone in adult male and female rats if the parathyroid hormone is gradually deprived. A greater ability of female rats to restore the calcium level, especially seen when thyroidectomized after adaptation to the lack of parathyroid hormone, suggests that estrogens play a significant role in the homeostatic control of serum calcium in chronic disorders in calcium regulation. Adult female rats born to parathyroidectomized mothers show a less marked fall in the serum calcium level following unilateral or bilateral parathyroidectomy as compared with that seen in intact adult females (Fujii, 1978). This finding suggests that the functional differentiation of organs which regulate calcium metabolism is affected by the uterine environment supplied with the blood of low calcium. It is well established that parathyroid hormone, calcitonin and metabolites of vitamin D3 play a major role in the homeostatic control of serum calcium. Bone, kidney and intestine have been considered to be responsible for the regulation of serum calcim level (for Review see Copp, 1974). However, precise interrelationship among organs involved in calcium homeostasis is still unclear. The present experiment was carried out to study the time course of the adaptation Received March9, 1979. 138 FUJII AND MORITA Endocrinol. Japon. April1980 of the regulatory system of serum calcium to the lack of parathyroid hormone in intact adult rats. A gradual decrease in the serum calcium level was induced by stepwise removal of parathyroid gland with various time intervals. Serum calcium level was used as a parameter of alteration of calcium homeostasis. In addition, the effect of thyroidectomy was also studied in order to know the contribution of both thyrocalcitonin (calcitonin) and thyroid hormones in adaptation of calcium metabolism to the lack of parathyroid hormones. Materials and Methods Adult male rats, weighing300-350g, and female rats, weighing230-260g, of the inbred Wistar-Imamichi strain, were obtained from the Animal Breeding Laboratory (Ohmiya, Saitama Prefecture) and kept in our laboratory at least one week before use. In the first experiment, male and female rats were subjected to unilateral parathyroidectomy and then the rest of their parathyroid gland was removed72hr, one or six weeks later. Bilateral thyroid glands in rats of these three groups were removed10weeks after the second unilateral parathyroidectomy. In the second experiment, rats of both sexes were divided into two groups; one group received simultaneous bilateral parathyroidectomy and was followed by bilateral thyroidectomy one week later; another group received simultaneous bilateral thyroparathyroidectomy. Control animals were sham-operated twice with a time interval of one week. The surgical parathyroidectomy or thyroidectomy in all experimental groups were performed under ether anesthesia, starting around0930a. m. for all experimental groups. All animals were given stock diet (Calcium, 1.01%; phosphorus, 1.17%, Oriental Yeast Co. Ltd., Tokyo) and tap water ad libitum and kept in a temperature-controlled room (21-25•Ž) with a lighting schedule of14hr light (0600a. m.-0800 p. m.) and 10hr darkness. A branch of the saphenous vein of the hind-limb was punctured by a22-gauge needle and blood samples were collected 2, 6, 10, 24, 48and 72hr and7days after each operation without anesthesia. The sera isolated were stored at-20•Ž until analyzed. Calcium concentration was determined using a Hitachi atomic absorption spectrometer. Serum protein was measured by the method of Lowry et al. (1951). The statistical analyses employed were Studen's t test; P<0.05was considered to be sig-