This introduces us to an important general principle—the spe cific reactivity of tissues to hormones. Thyroid from any verte brate will act upon Amphibia ; but corresponding tissues in frog and newt will react differently to the same thyroid. The same is true of the tail; in Anura thyroid causes its total resorption, in Urodela only that of its fin-membrane. The tail of Amphibia also illustrates the principle of differential susceptibility. The limbs of frog tadpoles begin excess growth when the least trace of thyroid extract is to be found in the blood : the tail is not resorbed until a considerable threshold-concentration is attained.
Specific reactivity is also illustrated by the neotenous Amphibia, i.e., those which normally live their whole lives and reproduce while retaining larval form and aquatic habit. Most of these m cannot be artificially metamorphosed even by the heaviest doses of thyroid : their tissues no longer react to the hormone. In Amblystoma matters are different. Most species metamorphose normally. The well-known axolotl of Old Mexico, however, is neotenous. It has now been shown that thyroid will always meta morphose axolotls. There is, however, a threshold dose below which only minor, reversible changes occur. A dose just near the threshold causes metamorphosis to advance rather more than half-way and then stop, leaving the animal neither aquatic nor terrestrial. Metamorphosis is thus not an "all-or-nothing" phe nomenon. Neoteny here is apparently due to three co-operating factors: (I) failure of the thyroid's "release mechanism," (2) reduced thyroid-size, (3) reduced tissue-sensitivity.
The thyroid, however, is not the only ductless gland concerned in metamorphosis. The pituitary also plays an important, if sec ondary, role. Its secretion is indeed necessary for the develop ment of the thyroid ; tadpoles with pituitary removed never meta morphose, and their thyroid-size is less than of normal. Its own secretion can also produce metamorphosis, in axolotls as well as tadpoles, even in animals deprived of their own thyroid and pituitary. However, the hormone is not so potent as that of the thyroid. These effects are all due to the anterior lobe. The posterior lobe produces a hormone which if injected in sufficient quantity will antagonize small doses of thyroid or moderate doses of anterior pituitary, and so prevent metamorphosis.
We must briefly mention some points concerning the time-rela tions of metamorphosis. The common European frog, Rana tem poraria, normally takes about four months to metamorphose; some toads only four to six weeks ; the American leopard-frog over a year ; and several bull-frogs over two years. The thyroid of leopard-frog or bull-frog tadpoles contains the metamorphosis hormone, since if engrafted into tadpoles of other species it in duces rapid metamorphosis. Apparently the prolongation of larval life in these animals is due to an alteration in the relative rates of thyroid-growth and body-growth. A definite concentration of thyroid hormone in the blood must be reached before metamor phosis can occur. If the thyroid grows relatively more slowly, metamorphosis will be postponed. The same postponement could equally well be effected by diminished sensitivity of the tissues to thyroid. Thus the relative rate of thyroid-growth and the absolute degree of tissue sensitivity between them decide the date of metamorphosis.
The compensatory reactions of the thyroid are interesting. At high temperatures, a tadpole's thyroid diminishes in size and activity, at low temperatures it increases. Similarly, after a small dose of thyroid, the animal's own gland is not called upon, and shrinks. Interesting results have been obtained by utilizing these facts. If tadpoles are kept at high temperatures till half grown, and then placed at low temperature, they fail to meta morphose. This is because their thyroids, first much reduced by heat, are unable to respond to the extreme demands made on them by cold, and can only react by forming a goitre which vainly tries to compensate by quantity of tissue for lack of quality of secretion.
Again, if half-grown normal tadpoles are put at very low and very high temperatures after receiving a small dose of thyroid, those at high temperature will metamorphose in under 48 hours, but those at low will proceed half-way with metamorphosis, and remain thus even if put at medium temperature. The dose of thyroid was sufficient to cause their own thyroid to shut down its activity, but not sufficient to counteract the cold.
It should be mentioned that Romeis claims to have achieved a definite influence on the date of metamorphosis by immersing frog eggs or sperm in thyroid solutions.