title: Luteinizing hormone-releasing hormone (LHRH) receptors in the neuroendocrine-immune network. Biochemical bases and implications for reproductive physiopathology.
abstract: It seems apparent that the brain-pituitary-reproductive axis and the brain-thymus-lymphoid axis are linked by an array of internal mechanisms of communication that use similar signals (neurotransmitters, peptides, growth factors, hormones) acting on similar recognition targets. Moreover, such communication networks form the basis and control of each step and every level of reproductive physiology. This work has focused on the LHRH system, a primary central and peripheral clock of both neuroendocrine and immune functions. From the initiation of a sexually organized response, the detection of sexual odors, and the induction of mating behavior, extrahypothalamic and hypothalamic LHRH orchestrates the neuroendocrine modulation of gonadotropin secretion, while its expression within the ovary directly controls specific events such as follicular atresia. The presence of LHRH receptors in oocytes clearly anticipates a potential action of the decapeptide during the process of fertilization and/or implantation. Within the thymus and other peripheral immune organs, LHRH plays a unique role of immunomodulator, contributing to the sex-dependent changes in immune responsiveness during the estrous-menstrual cycle as well as pregnancy. The reciprocity of the neuroendocrine-immune signaling systems is further supported by the ability of sex steroids to modulate thymus-dependent immune functions via direct effects on specific target genes involved in the development of sex dimorphism and sex-dimorphic immune responses, including the downregulation of immune response observed during pregnancy. Such cyclic changes in immune responsiveness could have a physiological implication, such as the decrease or suppression in cell-mediated immunity observed in the postovulatory phase of the cycle and in pregnancy, respectively, and might play a role during the implantation process and the establishment of pregnancy. In this context, the ability of corticosterone to directly inhibit both GR transcript levels as well as a cell-mediated immune response within the thymus, and the modulation of such an inhibitory effect by the sex steroid hormone milieu, may offer an explanation and a molecular mechanism whereby stress may be deleterious for reproduction, also via immunomodulation. On the other hand, hormonally mediated alterations in immunity might also have a pathological implication in sexually related immune diseases. For example, in mouse and humans, lupus erythematosus is more prevalent in females and estrogen accelerates the disease process, while menstruation is known to exacerbate idiopathic thrombocytopenia purpura. Sex steroid hormone milieu might also have a role in controlling the stress response through immunomodulation. Within the placenta, an intricate network of signaling systems controls a delicate interplay between the neuroendocrine hormones, growth factors, and cytokines that are susceptible to play a major local role in the processes of implantation and the establishment and completion of pregnancy. The neuroendocrine and immunomodulatory role of LHRH continues well after parturition because the presence of LHRH-like material within the mammary gland and milk participates in the physiological modulation of hypophyseal, gonadal, and immune functions of the pups. Such a significant role played by the hypothalamic peptide in the modulation of immune responsiveness would indicate LHRH as the signal conveying information to both neuroendocrine and immune cells, with the role of informing and then transducing the messages into appropriate biological responses.(ABSTRACT TRUNCATED)
authors.affiliation: Department of Pharmacology, University of Catania Medical School, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Marchetti
authors.forename: F
authors.initials: F
authors.lastname: Gallo
authors.forename: Z
authors.initials: Z
authors.lastname: Farinella
authors.forename: C
authors.initials: C
authors.lastname: Romeo
authors.forename: M C
authors.initials: MC
authors.lastname: Morale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000502:physiology / Q000648:ultrastructure; D007107:Immune System / Q000502:physiology* / Q000648:ultrastructure; D007246:Infertility / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000502:physiology* / Q000648:ultrastructure; D010053:Ovary / Q000502:physiology / Q000648:ultrastructure; D010902:Pituitary Gland / Q000502:physiology / Q000648:ultrastructure; D011247:Pregnancy; D011966:Receptors, LHRH / Q000502:physiology*; D012098:Reproduction / Q000502:physiology*
chemical_list: D011966:Receptors, LHRH