Hypothalamic Control of Mitogen-Induced Proliferative Responses and Luteinizing Hormone-Releasing Hormone Levels in Thymus and Peripheral Blood of Rat Fetuses

Abstract

The role of endogenous luteinizing hormone-releasing hormone (LHRH) in the development of concanavalin A (ConA)-induced proliferative responses was studied in rat fetuses. Preliminary treatment of fetuses in utero with either the LHRH receptor antagonist or anti-LHRH antibodies resulted in the suppression of ConA-induced proliferative responses of thymocytes. LHRH and LHRH-immunopositive cells, morphologically similar to thymocytes, were detected in intact fetal thymus. A significant content of LHRH was also found in the peripheral blood of fetuses. The LHRH content in thymus and plasma was similar in males and females. Surgical ablation of the hypothalamus resulted in 2-fold decreases in thymus and plasma levels of LHRH in 21-day-old fetuses compared to sham-operated fetuses. It was concluded that LHRH regulates mitogen-induced proliferative responses of thymocytes during prenatal ontogenesis in the rat. The main source of plasma LHRH at that period is the hypothalamus. Moreover, LHRH is synthesized in the fetal thymus. Thus, LHRH is suggested to have not only a central effect but also to be involved in autocrine or paracrine regulation of proliferative immune responses.

Interactions Between Reproductive and Immune Systems During Ontogeny: Roles of GnRH, Sex Steroids, and Immunomediators

“…It is considered that sex steroids modulate molecular processing of the GnRH precursor, with its processing in the thymus differing from that in the hypothalamus. The results of our experiments exhibit that GnRH is also synthesized in the fetal thymus (Zakharova et al, 2005). Immunocytochemical analysis for GnRH in the thymus of 21-day rat fetuses revealed the presence of GnRH-positive cells morphologically identical to thymocytes.…”

“…GnRH2 and GnRH3 supposedly function as neuromodulators, the former being involved in the regulation of sexual behavior and the latter, in the integration of olfactory signals and other processes related to reproduction. Extracerebral synthesis is characteristic mainly of GnRH2, which has been revealed in the thymus, spleen, ovaries, testes, prostate, mammary gland, and placenta (Jacobson et al, 2000;Zakharova et al, 2005). Along with hypothalamic GnRH, extracerebral GnRH2 plays a role in the development and functioning of the immune system at different stages of ontogeny (Morale et al, 1991;Zakharova et al, 2005).…”

“…Extracerebral synthesis is characteristic mainly of GnRH2, which has been revealed in the thymus, spleen, ovaries, testes, prostate, mammary gland, and placenta (Jacobson et al, 2000;Zakharova et al, 2005). Along with hypothalamic GnRH, extracerebral GnRH2 plays a role in the development and functioning of the immune system at different stages of ontogeny (Morale et al, 1991;Zakharova et al, 2005). According to Marchetti et al (1998), GnRH is one of the most important signal molecules involved in the neuroendocrine-immune interaction.…”

Plasticity of neuroendocrine and immune systems in early development

“…The administration of testosterone to castrated animals leads to a rapid decrease in the thymus weight as a result of activation of apoptosis (Olsen and Kovacs, 2001). One of the possible mechanisms underlying these processes is an increase in the content of gonadotropin releasing hor mone (GnRH) in the thymus, which stimulates the proliferation of thymocytes (Zakharova et al, 2000(Zakharova et al, , 2005. Sex steroids modulate the processing of the GnRH precursor, the content of which in the thymus is much higher than in the hypothalamus.…”

The role of serotonin in the immune system development and functioning during ontogenesis

“…Their effects on the immune system are nonspecific, brief, and reversible. In early ontogenesis, they induce development and have an irreversible morphogenetic influence on the fetus, both within the central nervous system and on periph eral organs (Fowden and Forhead, 2004;Zakharova et al, 2005;Spencer et al, 2011).…”