Adrenomedullin 2/intermedin in the hypothalamo-pituitary-adrenal axis.
Adrenomedullin 2/intermedin (AM2/IMD) is a new member of the calcitonin/calcitonin gene-related peptide (CGRP) family. CGRP, adrenomedullin (AM), and AM2/IMD share the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP). The CRLR/RAMP2 or CRLR/RAMP3 complex forms the AM receptor, whereas the CRLR/RAMP1 forms the CGRP receptor. AM2/IMD binds non-selectively to all three CRLR/RAMP complexes. AM2/IMD has various actions, such as a potent vasodilator action and a protective action against oxidative stress, like AM and CGRP. When administered intracerebroventricularly, AM2/IMD stimulates the sympathetic nervous system and increases blood pressure. In human hypothalamus, AM2/IMD is expressed in the paraventricular and supraoptic nuclei and colocalized with arginine vasopressin. Anterior pituitary cells were diffusely immunostained for AM2/IMD. AM2/IMD stimulates the release of ACTH, prolactin, and oxytocin, but suppresses GH release. Some of these pituitary actions of AM2/IMD have been supposed to be mediated by an unidentified unique receptor for AM2/IMD. In the adrenal gland, immunoreactive (IR)-AM2/IMD and IR-AM were detected in the medulla, while the degree of IR-AM2/IMD and IR-AM in the cortex was relatively weak or undetectable. Furthermore, AM2/IMD and AM were expressed in adrenocortical tumors, such as aldosterone-secreting adenomas, and pheochromocytomas. CRLR and RAMPs are expressed in the hypothalamus, pituitaries, adrenal glands, and adrenal tumors. Thus, AM2/IMD is expressed in every endocrine organ of the hypothalamo-pituitary-adrenal axis together with its receptor. AM2/IMD may act as a neurotransmitter or modulator in the brain and as a paracrine/autocrine regulator in the hypothalamo-pituitary-adrenal axis.
Takahashi
Kazuhiro
K
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. ktaka-md@med.tohoku.ac.jp
Morimoto
Ryo
R
Hirose
Takuo
T
Satoh
Fumitoshi
F
Totsune
Kazuhito
K
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000033:anatomy & histology / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000033:anatomy & histology / Q000502:physiology*; D058261:Receptor Activity-Modifying Proteins / Q000235:genetics / Q000378:metabolism; D058265:Receptors, Adrenomedullin / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
C484330:ADM2 protein, human; D058286:Calcitonin Receptor-Like Protein; D046912:Multiprotein Complexes; D036361:Peptide Hormones; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin