Luteinizing hormone-releasing hormone (LHRH) receptors in the neuroendocrine-immune network. Biochemical bases and implications for reproductive physiopathology

• Published in: Annals of the New York Academy of Sciences 1996-04, Vol.784 (1), p.209-236
• Main Authors: Marchetti, B, Gallo, F, Farinella, Z, Romeo, C, Morale, M C
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Female; Humans; Hypothalamus - physiology; Hypothalamus - ultrastructure; Immune System - physiology; Immune System - ultrastructure; Infertility - physiopathology; Male; Molecular Sequence Data; Neurosecretory Systems - physiology; Neurosecretory Systems - ultrastructure; Ovary - physiology; Ovary - ultrastructure; Pituitary Gland - physiology; Pituitary Gland - ultrastructure; Pregnancy; Receptors, LHRH - physiology; Reproduction - physiology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.1996.tb16238.x

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 prevale