Tachykinins and the hypothalamo–pituitary–gonadal axis: an update

Tachykinins play a critical role in neuroendocrine regulation of reproduction. The best known members of the family are substance P (SP), neurokinin A and neurokinin B. Tachykinins mediate their biological actions through three G protein-coupled receptors, named NK1, NK2, and NK3. SP was suggested to play an important role in the ovulatory process in mammals and humans. Recent findings suggest a role of tachykinins in the aging of the hypothalamo–pituitary–gonadal axis. A high presence of SP was found in the sheep pars tuberalis and evidence indicates that it may have some role in the control of prolactin secretion. The presence of SP was confirmed in Leydig cells of the rat testes of animals submitted to constant light or treated with estrogens. Tachykinins were found to increase the motility of human spermatozoa. Tachykinins were also found to be present in the mouse ovary and more specifically, in the granulose cells. It is possible that tachykinins may play an important role in the ovarian function. NKB has been implicated in the steroid feedback control of GnRH release. Human mutations in the gene encoding this peptide or its receptor (TACR3) lead to a defect in the control of GnRH. A specific subset of neurons in the arcuate nucleus of the hypothalamus, colocalized three neuropeptides, kisspeptin, NKB and dynorphin. This subpopulation of neurons mediates the gonadal hormone feedback control of GnRH secretion. NKB/NK3 signaling plays a role in puberty onset and fertility in humans. This minireview summarizes the recent data about the action of tachykinins on the hypothalamo–pituitary–gonadal axis.Fil: Lasaga, Mercedes Isabel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Debeljuk, Luciano. Southern Illinois University; Estados Unido

Antiserum to LH-RH Blocks Haloperidol-Induced Hyperprolactinemia in Female Rats

We investigated the effect of blocking endogenous LH-RH, by injection of anti-LH-RH sera, on serum prolactin levels previously elevated by treatment with haloperidol for 5 days. An acute intravenous injection of rabbit anti-LH-RH serum significantly reduced serum LH levels and blocked the hyperprolactinemia induced by haloperidol. In another group of rats, sheep anti-LH-RH serum induced a significant decrease of serum LH and also lowered serum prolactin levels previously elevated by haloperidol. In ovariectomized rats, sheep anti-LH-RH serum markedly reduced serum LH levels and also decreased serum prolactin elevated by the pretreatment with haloperidol. It is concluded that the blocking of endogenous LH-RH action results in a decreased release of prolactin in response to stimuli like haloperidol. These results support the possible existence of a paracrine interaction between the pituitary gonadotrophs and lactotrophs

Role of α-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation

Inflammatory processes contribute widely to the development of neurodegenerative  diseases. The expression of many inflammatory mediators was found to be increased in central nervous system (CNS) disorders suggesting that these molecules are major contributors to neuronal damages. Melanocortins are neuropeptides that have been implicated in a wide range of physiological processes. The melanocortin alpha-melanocyte stimulating hormone (a-MSH) has pleiotropic functions and exerts potent anti-inflammatory actions by antagonizing the effects of pro-inflammatory cytokines and by decreasing important inflammatory mediators. Five subtypes of melanocortin receptors (MC1R-MC3R) have been identified. Of these, the MC4 receptor is expressed predominantly throughout the CNS. Evidence of effectiveness of selective MC4R agonists in modulating inflammatory processes and their low toxicity suggest that these molecules may be useful in the treatment of CNS disorders with an inflammatory component. This review describes the involvement of the MC4R in central anti-inflammatory effects of melanocortins and discusses the potencial value of MC4R agonists for the treatment of inflammatory-related disorders.Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Debeljuk, Luciano. Southern Illinois University Estados Unidos; Estados UnidosFil: Durand, Daniela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Scimonelli, Teresa Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin