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Translational Research
Published in Goh Cheng Soon, Gerard Bodeker, Kishan Kariippanon, Healthy Ageing in Asia, 2022
Following treatment with DOI, FSHR and CYP19 mRNA expression in the rat ovaries determined by real-time PCR was significantly enhanced, with the maximal effect produced by DOI observed at 2.5 mg/kg. Rat ovarian protein kinase A mRNA expression was significantly increased by 72% in response to treatment with 10 mg/kg DOI.
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
FSH's biological effects are exerted through its binding to the FSH receptor (FSHR) (127). FSHR has been identified in the granulosa cells of the ovary, osteoclasts, osteoclast precursors, and mesenchymal stem cells (128). In addition, low FSHR levels are expressed by the endothelial cells of the ovaries. FSHR belongs to the subfamily of Gs protein–coupled receptors having seven transmembrane segments. FSHR comprises three domains: a large extracellular N-terminal domain (or ligand-binding domain), a transmembrane domain with seven transmembrane segments, and an intracellular C-terminal domain (128). The interaction between FSH and FSHR is due to the N-terminal domain of the receptor. The phosphorylation of cAMP response element-binding (CREB) and protein kinase A (PKA) is the signaling pathway that is mainly induced by FSH. However, the mitogen-activated protein kinase pathway has also been considered to be activated by FSH (129).
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
FSH is a 35.5 kDa glycoprotein hormone consisting of two subunits, alpha and beta, which are held together by non-covalent bonds [62]. Its overall structure is similar to those of LH, TSH and human chorionic gonadotropin (hCG), a product of the placenta during pregnancy. The alpha subunits of all four glycoprotein hormones are identical and consist of 96 amino acids, while the beta subunits vary. Both subunits are required for the biological activity of each hormone. FSH has a beta subunit of 111 amino acids that confers its specific biologic action and is responsible for interaction of the hormone with the FSH receptor (FSHR). The carbohydrate moiety of FSH is covalently bound to asparagine, and is composed of N-acetyl-galactosamine, mannose, N-acetyl-glucosamine, galactose, and sialic acid.
Mutational analysis of minichromosome maintenance complex component (MCM) family genes in Chinese Han women with polycystic ovarian syndrome
Published in Gynecological Endocrinology, 2023
Jiangyan Zhou, Faying Liu, Lifeng Tian, Ming Yang, Jun Tan, Xianxian Liu, Peishuang Li, Jia Chen, Ge Chen, Lixian Xu, Lisha Peng, Qiongfang Wu, Yang Zou
The minichromosome maintenance (MCM) family is highly conserved in vertebrates and comprises MCM2 through MCM10. These proteins play essential roles in DNA replication and cell cycle progression. Indeed, MCM proteins not only interact with S-phase checkpoint regulators, but also with components of DNA repair pathway [14–16]. The MCM 2-7 complex is instrumental for cell-cycle control, an operation that occurs during the G1 and G2 phases of mitosis [14,15]. MCM8 complexes with MCM9 and has a role in DNA repair and genome instability [17–19]. MCM10 involves in DNA replication and chromosomal instability [16,20]. Recently, studies showed that dysfunctional mutations in MCM8 and MCM9 could lead to premature ovarian failure (POF) and primary ovarian insufficiency (POI) [19,21–23]. Considering the shared biological features between POF/POI and PCOS, such as dysregulation of steroid hormones, and ovarian dysfunction, moreover, some mutations in POF/POI also exist in PCOS, such as AMH, FSHR, GDF9, and BMP15 [24–26], thus, we speculate that mutations/rare variants of MCMs might exist in Chinese patients with PCOS.
Heterochromatin extension: a possible cytogenetic fate of primary amenorrhea along with normal karyotype
Published in Journal of Obstetrics and Gynaecology, 2022
Bishal Kumar Dey, Shanoli Ghosh, Ajanta Halder, Somajita Chakraborty, Sanchita Roy
DNA that was extracted from the blood, contained the gene of interest. The gene of interest is follicle-stimulating hormone receptor (FSHR). This gene defect is related to primary ovarian failure (POF) which can be diagnosed during the detection of amenorrhoea. Depending on the data from review article, we performed the sequencing to check whether any FSHR’s variant is present or not in case of PA. Here, the gene was being captured using a custom capture kit. Illumina sequencing was used to sequence greater than 80–100× of the genome as well as whole exome. GATK best practices framework was used to identify the variants in the sample with the help of Sentieon (v201808.07) (Freed et al. 2017). The obtained sequence was aligned with human reference genome (GRCh38.13). The annotation of gene of the variants was performed using VEP program (McLaren et al. 2010) against the Ensemble release 99 human gene model (Zerbino et al. 2018). Exome Depth (v1.1.10) method was very useful to detect single-nucleotide variants (SNVs) and small indels and copy number variants (CNVs). With the help of this algorithm, detection of the CNVs was done based on comparison of the read-depths of the test data with the matched aggregate reference dataset.
Current and experimental drug therapy for the treatment of polycystic ovarian syndrome
Published in Expert Opinion on Investigational Drugs, 2020
Luigi Della Corte, Virginia Foreste, Fabio Barra, Claudio Gustavino, Franco Alessandri, Maria Grazia Centurioni, Simone Ferrero, Giuseppe Bifulco, Pierluigi Giampaolino
The gonadotropins, such as recombinant follicle-stimulating hormone (FSHr) or human menopausal gonadotropin (HMG), are another therapeutic option for women affected by PCOS [34,35]. These drugs represent the second-line treatment of infertility in anovulatory patients with PCOS undergoing timed intercourse or intrauterine insemination (IUI). The traditional standard step-up regimens [34] were replaced by either low-dose step-up regimens (consisting of a low starting dose FSH at 52.5 IU, continued with this same dose up to 14 days, but, if necessary, small stepwise increments in subsequent dosage can be done) [35], or step-down regimens (with an initial dose of FSH at 1.5 and 2.5 ampoules – 75 I.U/day, dependent on body weight, and decreasing steps of 0.5 ampoules/day based on sonographic findings) [36]. When using gonadotropin to stimulate the development of a single dominant follicle, it is difficult to choose the starting dose. It is essential to carefully monitor follicular development by ultrasound, also to reduce the risks of multiple pregnancy and OHSS; human Chorionic Gonadotropin (hCG) should not be administered if a total of three or more follicles larger than 14 mm in diameter have developed. Thus, in women with PCOS, the use of gonadotropins should be done with appropriate monitoring that minimizes the risk of multiple pregnancies [37].