Neuropeptide Glutamic Acid-Isoleucine May Induce Luteinizing Hormone Secretion via Multiple Pathways

Abstract

Neuropeptide glutamic acid-isoleucine (NEI) is a 14-amino acid peptide processed from prepro-melanin-concentrating hormone (ppMCH). In males, the localization of NEI is almost identical to that of MCH, the cell bodies of both being located primarily in the lateral hypothalamic area and zona incerta, projecting fibers throughout the brain. Although MCH has been widely studied, the role that NEI plays in brain circuitry has been poorly investigated. Recently, we showed that intracerebroventricular injection of NEI increases serum luteinizing hormone (LH) levels. In order to identify the anatomical substrate underlying this effect, we used combined immunohistochemistry methods to analyze the forebrains of females on the diestrus and proestrus days, as well as those of ovariectomized females treated with estradiol benzoate, with estradiol benzoate plus progesterone or with sesame oil (control animals). We found that ovariectomized females with no steroid treatment showed an increased number of NEI-immunoreactive neurons in the medial zona incerta. In addition, we observed dense to moderate NEI innervation of areas related to reproduction, including the organum vasculosum of the lamina terminalis, the anteroventral periventricular nucleus (AVPV) and the median eminence. The NEI fibers were in close apposition with the AVPV and gonadotropin-releasing hormone (GnRH) neurons expressing Fos in the afternoon of the proestrus day or following administration of estradiol benzoate plus progesterone. In the median eminence, NEI varicosities and terminal-like structures were in close proximity to blood vessels and GnRH fibers. Our results suggest that NEI might induce LH secretion in one of the following ways: by direct release into the median eminence, by modulation of GnRH neurons located in the preoptic area, by modulation of the GnRH terminals located in the median eminence or by an additive effect involving other neurotransmitters or neurohormones. Release of NEI might also induce LH secretion indirectly by modulating AVPV neurons.

Determination of acidic dissociation constants of glutamine and isoleucine in water using ab initio methods

“…The first ionization constant for isoleucine is obtained from combining equations (7) and (11) and is shown in equation (12). (12) It is evident that:…”

“…Recent studies have shown that Ile may be useful in the treatment of metabolic syndrome, diabetes, adiposity, and hepatic encephalopathy [8][9][10]. Furthermore, Ile derivatives have been targeted for the development of drugs, such as (2S,3R,4S)-4-hydroxyisoleucine [11], neuropeptide glutamic acid-isoleucine [12], and N-methyl-4-isoleucine cyclosporine [13]. Traditionally, Ile has been extracted from animal tissues and produced through chemical synthesis.…”

The roles of melanin-concentrating hormone in energy balance and reproductive function: are they connected?

“…MCH may directly innervate GNRH neurones which express ESR2 (ERb) (Herbison & Pape 2001), and/or indirectly via an interneurone that is both MCH and oestrogen sensitive and in turn acts on GNRH. Clearly, the neurocircuitry controlling the hypothalamic-pituitary-gonadal axis is complex and other neuromodulators are known to be involved: leptin, serotonin, dopamine, kisspeptin and NEI have all, for example, been reported to stimulate gonadotrophin release (MacKenzie et al 1984, Vitale et al 1993, Yu et al 1997, Messager et al 2005, Attademo et al 2006. Precisely where MCH fits into this neurocircuitry is yet to be defined, and the proposed indirect effects of MCH on GNRH via other neuronal populations will be discussed further.…”

Influence of Neuropeptide – Glutamic Acid-Isoleucine (NEI) on LH Regulation

“…The MCH receptors are classified into five subtypes: MC1-R to MC5-R [28]. MCH stimulates gonadotropin-releasing hormone (GnRH) release from hypothalamic explants, and it is interesting to note that MCH affects the release of LH [23] in the female rat.…”

“…A group of female rats were perfused on day 15 postovariectomy; a second group received10 µg of estradiol benzoate and were perfused two days later and a third group received 10 µg of estradiol benzoate and two days later 40 µg of progesterone and were perfused 5 h after treatment. To mimic the manipulation of the animals, we used a fourth group of ovariectomized rats treated with sesame oil, and also used female intact rats at proestrus and diestrus [28].…”