Effect of leucogenenol, a thymothyroid hormone, on the growth of immature and neonatally thymectomized rats.

The reports of early investigators that growth is delayed by thymectomy of immature animals have been confirmed. Although growth is delayed by thymectomy, thymectomized animals approach asymptotically with age the same final weight as corresponding intact animals. Treatment with leucogenenol, a thymothyroid hormone, accelerates the rate of growth of immature neonatally thymectomized rats to that of normal rats. However, treatment with leucogenenol does not increase the rate of growth of normal rats. Treatment with leucogenenol does not change levels of growth hormone (GH) or thyroxine (T4) in the serum of either thymectomized or intact immature and adult rats. Neither is the depression in levels of serum leucogenenol that follows thymectomy associated with a change in serum levels of GH or T4. Thus it is apparent that levels of serum leucogenenol do not affect the rate of growth of immature animals by increasing serum levels of GH or T4. By analogy with the finding that treatment with leucogenenol increases the rate at which committed cells of the bone marrow and cells involved in the immune response develop into functional cells, it is suggested that the levels of serum leucogenenol are one of the factors that determine the rate at which types of body cells that make up bone and other body tissues develop from committed precursors.

Effect of leucogenenol, a thymothyroid hormone, on allograft rejection and hemolysin formation.

Recent investigations in this laboratory have established that daily treatment with leucogenenol, an enolic heterocyclic hormone synthesized by the thymus and/or thyroid, induces neonatally thymectomized mice that have accepted a skin allograft to reject this allograft in 7 to 14 days. Also, daily treatment with leucogenenol causes neonatally thymectomized mice to respond to challenge with sheep erythrocytes with the formation of normal titers of hemolysin. These results demonstrate that the hormone leucogenenol induces the development of those cells, absent in neonatally thymectomized mice, that are necessary for a normal immune response.

Effect of tumors on the concentration of leucogenenol in the serum of mice.

It was found that inoculation of several strains of mice with several types of tumor cells resulted, within 24 hr, in a significant decrease in the serum leucogenenol levels of the mice. Serum leucogenenol levels of the mice inoculated with tumors that are rejected become normal or temporarily above normal at approximately the time the tumor is observed to be rejected. Contrariwise, serum leucogenenol levels of mice inoculated with tumors that are not rejected remain at significantly lower than normal levels during the life of the mice. Unlike tumors, skin allografts increase serum leucogenenol levels. When tumors are rejected because of the previous immunization of the mice, serum leucogenenol levels become normal at approximately the time the tumor is observed to be rejected. Excision of the tumor after 1 week of growth, with the consequent recovery of the mice, is accompanied by a recovery of normal serum leucogenenol levels. Also, it was found that injection of mice with a cell-free 0.9% NaCl solution extract of a tumor results in a temporary decrease in serum leucogenenol levels comparable to that observed with the inoculation of a viable tumor which lasts from 24 to 96 hr. It is suggested that the suppression of serum leucogenenol levels is one of the factors responsible for the immunosuppression associated with a growing tumor.

Effect of skin or muscle incisions or the loss of blood on serum leucogenenol level.

It has been found that damage to a tissue of a rabbit or a rat, such as results from a skin incision or an incision through the skin and muscles into the abdominal cavity, is followed 24 hr later by a significant increase in the concentration of leucogenenol in the animal's serum. Likewise, loss of approximately one-quarter to one-half of the blood in the circulation of rabbits or rats causes an increase 24 hr later in the animals' serum leucogenenol concentration.

Association of leucogenenol with specific proteins in serum.

Determination of the concentration of leucogenenol in the IgM, IgG, albumin, and low molecular weight protein fractions of serum demonstrated that leucogenenol is found only in protein fractions of molecular weights in the range of IgM and IgG. Determination of the distribution of leucogenenol in chromatographically separated serum proteins showed that leucogenenol has a maximum concentration in the proteins intermediate between those with the molecular weights of IgM and IgG. Comparison of the ratio of effluent to void volumes with the ratios of known proteins suggest that the associated or carrier protein of leucogenenol has a molecular weight of approximately 3 x 10-5. When additional leucogenenol is added to serum it is found in the same protein fractions as the leucogenenol normally present, indicating that there is excess carrier protein for leucogenenol in the serum.