Dataset Information

LPS-induced inflammation potentiates the IL-1?-mediated reduction of LH secretion from the anterior pituitary explants.

ABSTRACT: Acting at the level of the brain, interleukin- (IL-)1 ? is considered to be one of the most potent downregulators of reproduction processes during immune/inflammatory challenge. IL-1 ? suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the luteinizing hormone (LH) release from the anterior pituitary (AP). However, the presence of IL-1 ? receptors in the AP suggests the possible direct action of this cytokine on LH secretion. The study was designed to determine the effect of IL-1 ? on the LH secretion from the AP explants collected from saline and LPS-treated ewes in the follicular phase. It was found that IL-1 ? suppressed (P ? 0.01) GnRH-stimulated LH release and LH ? gene expression in AP explants in both groups. However, IL-1 ? action was more potent in the explants collected from LPS-treated animals. Pituitaries from LPS-treated animals were characterized by increased (P ? 0.01) IL-1 type I receptor and decreased (P ? 0.01) GnRH receptor gene expression level compared to the saline-treated group. IL-1 ? also affected the GnRH-R gene expression in explants collected from LPS-treated animals. Our results show that direct action of IL-1 ? on the pituitary gonadotropes could be one of the reasons of the reproductive processes disorders accompanying an inflammatory state.

SUBMITTER: Herman AP

PROVIDER: S-EPMC3730224 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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LPS-induced inflammation potentiates the IL-1β-mediated reduction of LH secretion from the anterior pituitary explants.

Herman Andrzej Przemysław AP Krawczyńska Agata A Bochenek Joanna J Dobek Elżbieta E Herman Anna A Tomaszewska-Zaremba Dorota D

Clinical & developmental immunology 20130717

Acting at the level of the brain, interleukin- (IL-)1 β is considered to be one of the most potent downregulators of reproduction processes during immune/inflammatory challenge. IL-1 β suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the luteinizing hormone (LH) release from the anterior pituitary (AP). However, the presence of IL-1 β receptors in the AP suggests the possible direct action of this cytokine on LH secretion. The study ...[more]

PMID: 23956762

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Project description:Polycystic ovary syndrome (PCOS) is a hypothalamic-pituitary-gonadal (HPG) axis disorder. PCOS symptoms most likely result from a disturbance in the complex feedback regulation system of the HPG axis, which involves gonadotrophic hormones and ovarian steroid hormones. However, the nature of this complex and interconnecting feedback regulation makes it difficult to dissect the molecular mechanisms responsible for PCOS phenotypes. Global estrogen receptor α (ERα) knockout (KO) mice exhibit a disruption of the HPG axis, resulting in hormonal dysregulation in which female ERα KO mice have elevated levels of serum estradiol (E2), testosterone, and LH. The ERα KO females are anovulatory and develop cystic hemorrhagic ovaries that are thought to be due to persistently high circulating levels of LH from the pituitary. However, the role of ERα in the pituitary is still controversial because of the varied phenotypes reported in pituitary-specific ERα KO mouse models. Therefore, we developed a mouse model where ERα is reintroduced to be exclusively expressed in the pituitary on the background of a global ERα-null (PitERtgKO) mouse. Serum E2 and LH levels were normalized in PitERtgKO females and were comparable to wild-type serum levels. However, the ovaries of PitERtgKO adult mice displayed a more overt cystic and hemorrhagic phenotype when compared with ERα KO littermates. We determined that anomalous sporadic LH secretion caused the severe ovarian phenotype of PitERtgKO females. Our observations suggest that pituitary ERα is involved in the estrogen negative feedback regulation, whereas hypothalamic ERα is necessary for the precise control of LH secretion. Uncontrolled, irregular LH secretion may be the root cause of the cystic ovarian phenotype with similarities to PCOS.-Arao, Y., Hamilton, K. J., Wu, S.-P., Tsai, M.-J., DeMayo, F. J., Korach, K. S. Dysregulation of hypothalamic-pituitary estrogen receptor α-mediated signaling causes episodic LH secretion and cystic ovary.

Dataset Information

LPS-induced inflammation potentiates the IL-1?-mediated reduction of LH secretion from the anterior pituitary explants.

Publications

LPS-induced inflammation potentiates the IL-1β-mediated reduction of LH secretion from the anterior pituitary explants.

Similar Datasets

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