title: Corticosterone Blocks Ovarian Cyclicity and the LH Surge via Decreased Kisspeptin Neuron Activation in Female Mice.
abstract: Stress elicits activation of the hypothalamic-pituitary-adrenal axis, which leads to enhanced circulating glucocorticoids, as well as impaired gonadotropin secretion and ovarian cyclicity. Here, we tested the hypothesis that elevated, stress-levels of glucocorticoids disrupt ovarian cyclicity by interfering with the preovulatory sequence of endocrine events necessary for the LH surge. Ovarian cyclicity was monitored in female mice implanted with a cholesterol or corticosterone (Cort) pellet. Cort, but not cholesterol, arrested cyclicity in diestrus. Subsequent studies focused on the mechanism whereby Cort stalled the preovulatory sequence by assessing responsiveness to the positive feedback estradiol signal. Ovariectomized mice were treated with an LH surge-inducing estradiol implant, as well as Cort or cholesterol, and assessed several days later for LH levels on the evening of the anticipated surge. All cholesterol females showed a clear LH surge. At the time of the anticipated surge, LH levels were undetectable in Cort-treated females. In situ hybridization analyses the anteroventral periventricular nucleus revealed that Cort robustly suppressed the percentage of Kiss1 cells coexpressing cfos, as well as reduced the number of Kiss1 cells and amount of Kiss1 mRNA per cell, compared with expression in control brains. In addition, Cort blunted pituitary expression of the genes encoding the GnRH receptor and LHβ, indicating inhibition of gonadotropes during the blockage of the LH surge. Collectively, our findings support the hypothesis that physiological stress-levels of Cort disrupts ovarian cyclicity, in part, through disruption of positive feedback mechanisms at both the hypothalamic and pituitary levels which are necessary for generation of the preovulatory LH surge.
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Elena
authors.initials: E
authors.lastname: Luo
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Shannon B Z
authors.initials: SB
authors.lastname: Stephens
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Sharon
authors.initials: S
authors.lastname: Chaing
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Nagambika
authors.initials: N
authors.lastname: Munaganuru
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kauffman
authors.affiliation: Department of Reproductive Medicine and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674.
authors.forename: Kellie M
authors.initials: KM
authors.lastname: Breen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D004031:Diestrus / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D059648:Kisspeptins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D010053:Ovary; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011966:Receptors, LHRH / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004967:Estrogens; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D011966:Receptors, LHRH; D004958:Estradiol; D007986:Luteinizing Hormone; D003345:Corticosterone