THE THYROTROPIC HORMONE AND THE ANTIHORMONE PROBLEM1

Since the initial demonstrations (1, 2, 3) that injections of hypophyseal extracts containing thyrotropic hormone will induce marked activation of the thyroid gland, reports have been fairly uniform in stating that their excessive stimulation of the thyroid gland cannot be maintained much beyond 4 to 5 weeks (4 to 9), except in experiments with the duck (3, 10). The basal metabolic rate of the treated animals has been found to return to normal and the thyroid gland to become microscopically inactive upon continued treatment. Bruner and Starr (11) noted that when the decline in thyroid activity occurred, doses of extract up to 200 times the original did not restimulate the gland. Similar refractoriness has been shown to develop with the other hypophyseal hormones and the gonadotropic principle in pregnancy urine (12 to 15). Substances inhibitory to the thyrotropic hormone (7, 16) and also to the other hypophyseal principles (17, 18, 19) have been reported in the serum of refractory animals. To explain both the appearance of refractoriness and of an inhibitory substance in the serum, Collip (20) has proposed an antihormone theory, according to which every hormone is conceived to have an antihormone. According to this conception, it is this high titer of antihormone which makes the animals refractory. It has been demonstrated that no antihormone is formed against estrin (D’Amour, 21) so that Collip (22) has limited the applicability of the antihormone theory to the hormones of the hypophysis.