Effect of LPS on Reproductive System at the Level of the Pituitary of Anestrous Ewes

Abstract

In our research we focused our attention on the effect of the immune stress induced by bacterial endotoxin-lipopolysaccharide (LPS) on the hypothalamic-pituitary-gonadal axis (HPG) at the pituitary level. We examined the effect of intravenous (i.v.) LPS injection on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the anterior pituitary gland (AP) in anestrous ewes. The effect of endotoxin on prolactin and cortisol circulating levels was also determined. We also researched the effect of immune challenge on the previously mentioned pituitary hormones and their receptors genes expression in the AP. Our results demonstrate that i.v. LPS injection decreased the plasma concentration of LH (23%; p < 0.05) and stimulates cortisol (245%; p < 0.05) and prolactin (60%; p < 0.05) release but has no significant effect on the FSH release assayed during 6 h after LPS treatment in comparison with the control levels. The LPS administration affected the genes expression of gonadotropins' β-subunits, prolactin and their receptors in the AP. Endotoxin injection significantly decreased the LHβ and LH receptor (LHR) gene expression (60%, 64%; p < 0.01 respectively), increased the amount of mRNA encoding FSHβ, FSH receptor (FSHR) (124%, 0.05; 166%, p < 0.01; respectively), prolactin and prolactin receptor (PRLR) (50%, 47%, p < 0.01; respectively). The presented, results suggest that immune stress is a powerful modulator of the HPG axis at the pituitary level. The changes in LH secretion could be an effect of the processes occurring in the hypothalamus. However, the direct effect of immune mediators, prolactin, cortisol and other components of the hypothalamic pituitary-adrenal (HPA) axis on the activity of gonadotropes has to be considered as well. Those molecules could affect LH synthesis directly through a modulation at all stages of LHβ secretion as well as indirectly influencing the GnRHR expression and leading to reduced pituitary responsiveness to GnRH stimulation.

Effects of Central Injection of Anti-LPS Antibody and Blockade of TLR4 on GnRH/LH Secretion during Immunological Stress in Anestrous Ewes

“…Our study shows the inhibitory effect of LPS-induced immune stress on LH secretion in sheep which is consistent with previous in vivo studies conducted on anestrous ewes [15, 16]. Other researchers also showed that LPS affects LH secretion and even disturbs the preovulatory LH surge in ewes [29, 30].…”

“…It fully supports the previous studies reported about stimulatory effect of immune stress on cortisol release in various animal species including sheep [2, 16, 20, 43]. The elevation of the cortisol release suggests the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may result in inhibition of the HPG axis [2, 43].…”

“…In our earlier studies carried out on anestrous ewes, we showed that suppressive effect of LPS on GnRH/LH secretion occurs primarily at the level of hypothalamus, changing the gonadotropin-releasing hormone (GnRH) synthesis and release as well at the pituitary level by inhibiting release of LH from gonadotropic cells [15, 16]. …”

Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle

“…On the other hand, no effect of either AChE inhibitors or acute immune stress was found upon the circulating concentration of FSH. This also supports the results of previous studies indicating that acute inflammation did not influence the FSH release in both anoestrous [25] and follicular phase ewes [13]. However, other studies on ewes showed that the potency of LPS to affect the secretion of FSH may be dependent upon the duration of the inflammatory stimuli, because prolonged exposition of ewe on the action of bacterial endotoxin was found to disturb FSH release [3, 5].…”

“…The stimulatory effect of immune response on the release of cortisol and prolactin has been previously described in sheep [13, 25, 37]. Cortisol is considered as an important inhibitor of the HPG axis activity, targeting the LH release [37].…”