Effects of GnRH immunization on the reproductive axis and thymulin

Abstract

The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic-pituitary-gonadal (HPG) axis of rats immunized against GnRH remains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulin in vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization against GnRH in early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly on GnRH neurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.

Physiological interactions between the hypothalamic-pituitary-gonadal axis and spleen in rams actively immunized against GnRH

“…Given those, we determined GnRH synthesis in the hypothalamus. In consistent with our previous studies [24,37] and others [19,38] in rats, both immunocastration and surgical castration significantly reduced GnRH synthesis in the hypothalamus of rams, as both mRNA expressions of GnRH in the hypothalamus ARC and POA, as well as GnRH content in hypothalamic median eminence were markedly decreased. Reduced GnRH production from the hypothalamus would result in reduced immune functions if it could modulate immune system through endocrine pathways.…”

“…Whether the disrupted neuroendocrine function of HPG axis has an effect on immune system of GnRH-immunized animals is largely unknown. Most recently, using a rat model, two studies have focused on the effects of immunocastration on the interaction between HPG axis and thymus [18,19]. However, as for the largest secondary and most important immune organ, spleen, which contains about one-fourth of the body's lymphocytes and initiates immune responses to bloodborne antigens [20], currently there are no reports of the effects of immunocastration on the interaction between HPG axis and spleen.…”

Effect of GnRH immunocastration on immune function in male rats

“…In this study, we investigated the effects of immunocastration on the development and function of male rats' reproductive system and immune system. In agreement with previous studies (36,37,42), GnRH active immunization stimulated the production of antibodies 2 weeks after the first immunization, and resultantly reduced the concentration of serum testosterone remarkably, inhibited the development of testes and spermatogenesis over time.…”

“…In fact, recent researches have verified our hypothesis. When immunized against GnRH, thymulin was downregulated in early stage and subsequently upregulated in male rats (36). Accordingly, T lymphocytes differentiation in the thymus was repressed in early stage, and then restored and enhanced at later time points (37).…”

The Immunoendocrine Thymus as a Pacemaker of Lifespan

“…Thymosin F5 increased corticotropin, beta-endorphin, and cortisol level in monkeys [35], and thymectomy decreased the level of these hormones. Increasing thymulin level enhances pituitary gonadotropin level, acting directly on GnRH neurons [36]. In vitro conditions, the stimulatory effect of thymosin beta 4 on the production of LHRH and LH by hypothalamic and pituitary tissues was observed [34,37].…”