The brain synthesizes steroids de novo, especially progesterone. Recently estradiol has been shown to stimulate progesterone synthesis in the hypothalamus and enriched astrocyte cultures derived from neonatal cortex. Estradiol-induced hypothalamic progesterone has been implicated in the control of the LH surge. The present studies were undertaken to determine whether hypothalamic astrocytes derived from female neonatal or female postpubertal rats increased production of progesterone in response to an estradiol challenge. Estradiol induced progesterone synthesis in postpubertal astrocytes but not neonatal astrocytes. This estradiol action was blocked by the estrogen receptor antagonist ICI 182,780. Previously we had demonstrated that estradiol stimulates a rapid increase in free cytosolic Ca(2+) ([Ca(2+)](i)) spikes in neonatal cortical astrocytes acting through a membrane estrogen receptor. We now report that estradiol also rapidly increased [Ca(2+)](i) spikes in hypothalamic astrocytes. The membrane-impermeable estradiol-BSA construct also induced [Ca(2+)](i) spikes. Both estradiol-BSA and estradiol were blocked by ICI 182,780. Depleting intracellular Ca(2+) stores prevented the estradiol-induced increased [Ca(2+)](i) spikes, whereas removing extracellular Ca(2+) did not prevent estradiol-induced [Ca(2+)](i) spikes. Together these results indicate that estradiol acts through a membrane-associated receptor to release intracellular stores of Ca(2+). Thapsigargin, used to mimicked the intracellular release of Ca(2+) by estradiol, increased progesterone synthesis, suggesting that estradiol-induced progesterone synthesis involves increases in [Ca(2+)](i). Estradiol treatment did not change levels of steroid acute regulatory protein, P450 side chain cleavage, 3beta-hydroxysteroid dehydrogenase, and sterol carrier protein-2 mRNAs as measured by quantitative RT-PCR, suggesting that in vitro, estradiol regulation of progesterone synthesis in astrocytes does not depend on transcription of new steroidogenic proteins. The present results are consistent with our hypothesis that estrogen-positive feedback regulating the LH surge involves stimulating local progesterone synthesis by hypothalamic astrocytes.
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http://dx.doi.org/10.1210/en.2006-0774 | DOI Listing |
Sci Rep
December 2024
Chinese Medicine Guangdong Laboratory, Hengqin, 519031, Guangdong, China.
HR/HER2-low breast cancer is a significant subgroup of conventional HR/HER2-negative breast cancer, and combination of CDK4/6 inhibitor and endocrine therapy is the standard first-line and second-line treatments for advanced HR/HER2-low breast cancer. Nevertheless, it remains uncertain whether HER2 signaling affects the effectiveness of CDK4/6 inhibitor administered in combination with endocrine therapy for HR/HER2-low breast cancer and suitable intervention measures. This study revealed poor efficacy for CDK4/6 inhibitor combined with endocrine therapy for HR/HER2-low breast cancer in vitro and in vivo models.
View Article and Find Full Text PDFVet Sci
December 2024
Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China.
(AMK) as an oriental medicine has been used in the treatment of threatened abortion. (AT-I) is one of the major bioactive components of AMK. This study aimed to investigate the effect of AT-I on the secretion of estradiol (E) and progesterone (P) in feline ovarian granulosa cells (FOGCs), which is necessary for pregnancy.
View Article and Find Full Text PDFVet Sci
December 2024
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.
Yak (), a special breed of cattle on the Qinghai-Tibet Plateau, has low fertility due to nutritional deficiency, especially the trace elements. The steroid hormones estradiol (E2) and progesterone (P4) synthesized by yak follicular granulosa cells (BGCs) are involved in the entire reproductive process. In the present study, we investigated the effects of trace elements and vitamins on yak follicular GCs, including the cellular activity, the synthesis of E2 and P4, and the expression of genes related to steroid hormone synthesis.
View Article and Find Full Text PDFToxins (Basel)
November 2024
Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary.
The effect of mycotoxin exposure on follicular fluid composition and reproductive outcomes in women undergoing in vitro fertilisation (IVF) was investigated in this study. Twenty-five patients were included, and follicular fluid and serum samples were analysed for various mycotoxins. Principal observations:1.
View Article and Find Full Text PDFCurr Oncol
December 2024
Grupo de Estudios Clínicos Oncológicos del Perú (GECOPERU), Lima 15038, Peru.
Advanced breast cancer is an incurable disease, with a median overall survival of 3 years, including in countries without access problems. Although chemotherapy is reserved in some cases, it is still used in many countries as a first-line therapy. The aim of our study is to evaluate the first-line treatment choices and the factors that influence therapeutic decisions.
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