FUNCTIONAL TRANSPLANTATION OF THE RAT PITUITARY-GLAND

OBJECTIVE: These studies evaluated the ability of transplanted pituita ry cells to restore pituitary function in hypophysectomized rats. METH ODS: The pituitary glands of neonatal Lewis rats were rapidly removed, enzymatically dispersed, and stereotactically introduced into the thi rd ventricle of hypophysectomized adult male Lewis rats. Four weeks af ter implantation, plasma levels of anterior pituitary hormones in impl anted animals were compared with those of sham-transplanted control an imals. RESULTS: Plasma levels of prolactin, growth hormone, thyroid-st imulating hormone, and beta-endorphin were below the range of detectio n in 14 sham-operated animals. In implanted animals, restitution of se rum prolactin occurred in 100% of the animals tested, with levels of 2 .6 +/- 1.0 ng/ml (mean +/- standard error of the mean; normal, 2-4 ng/ ml). Growth hormone was assayable in 71% of the animals, with a mean v alue of 29 +/- 13 ng/ml over all animals (normal, 1-100 ng/ml); thyroi d-stimulating hormone was restored in 68%, with mean resting levels of 79 +/- 13 ng/ml (normal, 100-400 ng/ml); luteinizing hormone levels w ere found in 53%, with mean levels over all animals of 0.2 +/- 0.1 ng/ ml (normal, 0.5-1.0 ng/ml); and beta-endorphin was restored in 45% to high vesting levels of 163 +/- 31 pg/ml (normal, 20-30 pg/ml). A chall enge with hypothalamic releasing factor and a cold stress test were pe rformed on the animals that had received transplants. Positive hormone responses to both of these tests suggested sensitivity of the pituita ry grafts to both endogenous and exogenous sources of stimulation. His tological sections of paraformaldehyde-fixed brains from implanted ani mals clearly demonstrated survival of clusters of grafted pituitary ce lls. Positive immunohistochemical staining for adrenocorticotropic hor mone and thyroid-stimulating hormone was demonstrated in sections of t he grafted tissue. CONCLUSION: These data suggest survival of neonatal pituitary transplants in the third ventricle of adult hypophysectomiz ed rats with concomitant restoration of anterior pituitary hormone fun ction.