| Citation | Dr. Charlton is distinguished for his contributions to the physiological analysis of the HPG (hypogonadal) mutant mouse. This mouse shows no gonadal development and has proved valuable for understanding how the hypothalamo-pituitary axis functions as an integrated unit. The research showed, firstly, that the abnormal mice have extremely low levels of pituitary gonadotrophins but that appropriate exogenour treatment with GnRH leads to full sexual maturation. Episodic, not continuous, treatment with GnRH is essential to restore the pituitary gland. He then located the genetic lesion within the brain by showing an absence of endogenous GnRH and, most significantly, was able to overcome this deficit by transplanting hypothalamic fragments from normal mice into the HPG mouse brain. These fully restored reproductive function and led to breeding in homozygous HPG mice. These hypothalamic transplants were among the first functionally successful brain transplants.
The system has been valuable as a simple assay for judging the success of a transplant and has led to a series of experiments on cerebral transplants showing that the groin is not an absolutely privileged site, that CNS tissues express Class I MHC molecules and that the site of a transplantation is relevant to the immunological response.
His earlier work on the hypothalamous-hypophyseal axis of the vole was significant in demonstrating rhythmic changes of hormone levels in the wild and in showing the involvement of the pineal in hymoral control. |