Age-related changes in adenohypophyses of mice with the hereditary obese hyperglycemic syndrome (ob/ob) in relation to the diabetic state of the animals.

Mice with hereditary, monogenic obese-hyperglycemic syndrome (ob/ob) were shown to have smaller adenohypophyses in comparison to their normal littermates from an age of 4 weeks onward. The size of the pars intermedia of obese mice was not, however, significantly different from that of normal littermates. Morphometric criteria strongly suggest hyperactivity of the cells of the pars intermedia of obese hyperglycemic mice. The enhanced secretion of bioactive peptides of the pars intermedia may contribute to the diabetic aspects of the obese-hyperglycemic syndrome. The hyperactivity of the pars intermedia is likely to be allophenic.

Congenital hypothyroidism in latent obese (ob/ob) mice.

Activity of thyroid glands in latent-obese baby mice is below that of normal ones from birth on. Maturation of certain features, such as pinnae freeing, eye and ear opening, eruption of lower incisor teeth, is delayed in latent obese mice. After thyroxin injections maturation is normalized. Data support the hypothesis that the obese hyperglycemic syndrome in mice is characterized by congenital hypothyroidism.

The role of hyperphagia and hypothyroidism in the development of the obese-hyperglycemic syndrome in mice (ob/ob).

Obese-hyperglycemic mice show hyperphagia and hypothyroidism. The reduced body temperature can be normalized by injection of thyroxin. Limiting food intake to normal non-obese levels reduces blood sugar level, insulin content of the blood and body weight. However, reduction of all these parameters together until normal level occurs only when combining thyroxin injection with restricted diet. Weight of epididymal fat pad, nuclear volume of Leydig cells and volumes of islets of Langerhans normalize too during the combined treatment. It is argued that in adult obese mice hyperphagia and hypothyroidism are two separate factors which cannot be completely compensated for one by another. At least some symptoms in the obese-hyperglycemic syndrome could be attributed to hypothalamic disturbances caused by a reduced thyroidal activity at a very early age after birth.

Brain deviations in adult obese-hyperglycemic mice (ob/ob).

In the brain of adult obese-hyperglycemic mice (ob/ob) deviations, such as reduced brain weight, diminished myelination, and reduced amount of DNA were found. These findings cannot be explained by hypothyroidism in adults since above mentioned deviations could only have been caused by a reduced thyroidal activity in the first weeks of postnatal life. Therefore, our data are in support of the earlier hypothesis of congenital hypothyroidism.

Development of the obese-hyperglycemic syndrome in mice with a growth hormone deficiency.

By mating mice heterozygous for the recessive gene, obese (ob/+) (+/+), with mice homozygous for the recessive gene, dwarf (+/+)(dw/dw), and subsequent mating of the offspring, mice homozygous for both the obese and dwarf gene were obtained. It was established that the genes for obese and dwarf mice belong to different linkage groups. The homozygous obese dwarf mice develop obesity and hyperinsulinemia. The degree of hyperglycemia developed by these homozygotes is not significantly different from that of nonobese dwarf mice. Because homozygous dwarf mice are deficient in growth hormone production, it was concluded that obesity and hyperinsulinemia can develop under conditions of extreme growth hormone deficiency.