Thyrotropin and α-Subunit in the Brain: Evidence for Biosynthesis within the Pituitary*

We have investigated whether TSH and α-subunit are present in the mouse central nervous system outside the pituitary gland. Using specific RIAs, TSH was detected at 2.0 ± 0.4 ngeq/g in the brain (excluding hypothalamus), 23 ± 3.1 ngeq/g in the hypothalamus, and 10,500 ± 1,800 ng-eq/g in the pituitary gland. For α-subunit, levels were 39 ± 0.9 ng/g in the brain (excluding hypothalamus), 419 ± 144 ng/g in the hypothalamus, and 154,000 ng/g in the pituitary. Posthypophysectomy, hypothalamic levels of TSH fell to the level detected in the rest of the brain, whereas a levels, although decreased, were still above those in the rest of the brain. To determine if alpha subunit was actually synthesized outside the pituitary gland, we assayed poly (A)-containing mRNA from the hypothalamus and the rest of the brain for the presence of mRNA coding for the α-subunit. Poly(A) mRNA was electrophoresed on agarose gels, transferred to nitrocellulose, and hybridized with a 32P-labeled α-subunit cDNA probe. We could detect no mRNA coding for the α-subunit in the brain or hypothalamus under conditions capable of detecting 3 and 14 copies/cell of α-subunit in the brain and hypothalamus, respectively, α mRNA was detectable in the pituitary under these conditions. Our findings are consistent with the hypothesis that TSH and α-subunit reach the brain by diffusion from the pituitary, though they do not exclude the possibility that TSH is synthesized in a very small proportion of brain cells.