Extrahypothalamic Thyrotropin Releasing Hormone (TRH) — Its distribution and its functions

On the neuropharmacology of thyrotropin releasing hormone (TRH).

Vascular casts of the pituitary gland have demonstrated a paucity of veins extending from the adenohypophysis to the systemic circulation and have suggested that some adenohypophyseal venous blood returns to the neurohypophysis. The neurohypophyseal capillary bed may function as a vascular switch and in this article a series of 14 questions are proposed regarding the vascular dynamics of the pituitary. Together these questions raise the larger question, namely, whether pituitary hormones are transported directly to the brain to modify brain function?

https://science.sciencemag.org/content/sci/204/4388/18.full.pdf

Pituitary-brain vascular relations: a new paradigm.

The presence of a hypothalamic hamartoma and precocious puberty in a 19-month-old boy provided an opportunity to study their relation. Excised tissue had the ultrastructural characteristics of an independent neuroendocrine unit -- i.e., neurons containing neurosecretory granules and blood vessels with fenestrated endothelium and double basement membranes. Immunofluorescence studies using specific antibody to luteinizing-hormone-releasing factor showed antigenicity to the factor in the hamartoma. The testicular-hypothalamic-pituitary axis was tested. Clomiphene unresponsiveness suggested a lack of maturation of central-nervous-system events characteristic of normal puberty. The negative feedback system between gonad and brain was intact but partially resistant to steroid suppression. These studies suggest that hypothalamic hamartomas may cause precocious puberty by autonomous production and release of luteinizing-hormone-releasing factor into vessels that communicate with the pituitary portal blood system.

Hypothalamic hamartoma: a source of luteinizing-hormone-releasing factor in precocious puberty.

Immunoreactive LHRH was detected in hypothalamic and extrahypothalamic brain extracts of the rat, bird (pigeon and chicken), reptile (tortoise and lizard), amphibian (frog and toad), teleost (cichlid), and elasmobranch (dogfish) and in the whole brain of the cyclostome (hagfish). The concentration of hypothalamic immunoreactive LHRH was more than 5-fold greater than that of the extrahypothalamic brain. Mammalian and amphibian hypothalamic immunoreactive LHRH yielded displacement curves parallel to those of synthetic LHRH in assays employing four antisera which recognize different regions of the decapeptide, thus suggesting a similarity in the structure of their LHRH. Hypothalamic immunoreactive LHRH from the bird, reptile, teleost, and elasmobranch differed from the mammalian and amphibian peptide in yielding displacement curves nonparallel to those of synthetic LHRH with three different antisera (1076, 743, and 744) which bind between Trp3 and Pro9 of LHRH. The difference in structure appears to be near ...

Comparative Aspects of Luteinizing Hormone-Releasing Hormone Structure and Function in Vertebrate Phylogeny

Publisher Summary This chapter discusses the distribution and effects of gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) in the central nervous system (CNS). The studies presented in the chapter provide evidence for the ubiquitous distribution of GnRH and TRH in extrahypothalamic regions of the rat nervous system, including the pineal gland, anterior pituitary, midbrain, cerebral and cerebellar cortices, and brain stem. TRH has also been demonstrated by radioimmunoassay in the rat spinal cord and in human cerebral spinal fluid. The heterogeneous distribution pattern of these peptides, found in greatest concentrations in hypothalamus and midbrain, corresponds with regions endowed with biogenic amines, inducing dopamine and norepinephrine. Hypothalamic peptides, such as melanocyte-inhibiting factor (MIF)-1, ProLeuGlyAmide, TRH, GnRH, and growth hormone-inhibiting hormone (GHIH), exert behavioral influences in animal bioassay models that do not depend on the integrity of the endocrine system. These have been exemplified by L-dopa potentiation in MIF-1, TRH, GnRH, and GHIH, serotonin potentiation in TRH and GnRH, reversal of barbiturate hypnosis in TRH, and protection against audiogenic seizures in GnRH. The direct application of three of these peptides, TRH, GnRH, and GHIH, on individual neurons at many levels of the rat CNS results in rapid and reversible suppression of action potentials, similar to the inhibitory effects of histamine and dopamine on identical neurons. Electrical stimulation of 134 tuberoinfundibular neuron axon terminals reveals efferent projections to unexpected areas of the CNS, including the anterior hypothalamic area, medial preoptic area, and the nucleus dorsalis medialis of the thalamus. These latter observations raise the possibility that these peptidergic neurons can be a potential source for hypothalamic peptides identified in the outer regions of median eminence.

Renaud L

Papers

Gonadotropin-releasing hormone and thyrotropin-releasing hormone: distribution and effects in the central nervous system.