Porcine thyrotropin releasing hormone, isolated from the hypothalamus, and synthetic L-(pyro)Glu-L-His-L-Pro(NH2) are biologically identical. (pyro)Glu-His-Pro(NH2) is active in vivo at 1 ng in mice. It stimulates TSH release from rat anterior pituitary glands in vitro. The in vivo and the in vitro responses are inhibited by ti'iiodothyronine. (pyro) Glu-His-Pro (NH2) raises plasma TSH levels in rats and mice as well as hypophysectomized rats with pituitary transplants under the renal capsule. When incubated in human serum it is inactivated, (pyro) Glu-His-Pro (NH2) is active orally as well as ip, iv and sc in mice. Minor modifications in the (pyro) Glu-His-Pro (NH 2 ) chemical structure decrease its biological activity. (Endocrinology 86: 1143(Endocrinology 86: , 1970 B OTH anatomical and physiological findings formed the basis for the concept of neurovascular control of anterior pituitary secretion. This concept was first formulated by G. W. Harris in the late forties at a time when many of the facts were obscure and the evidence circumstantial. Since that time many investigators have shown the uniqueness of this control system. Because of unsatisfactory methods for measuring TSH, investigators before 1948 were unable to prove that TSH secretion depended on hypothalamic function (1). Noteworthy are the subsequent physiologic studies performed by Greer (2), Bogdanove and Halmi (3), Brown-Grant, Harris and Reichlin (4), Ganong, Frederickson and Hume (5) and D'Angelo (6), which specifically demonstrated the hypothalamic control of TSH secretion. One of the important developments that had to emerge from the neurovascular concept was the isolation, structure and synthesis of the hypothalamic releasing hormones.
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