Role of hydroxysteroid (17beta) dehydrogenase type 1 in reproductive tissues and hormone-dependent diseases

Heinosalo, Taija; Saarinen, Niina M.; Poutanen, Matti

doi:10.1016/j.mce.2018.08.004

Cited by 18 publications

(12 citation statements)

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“…The hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) is a steroidogenic enzyme encoded by HSD17B1 gene, to efficiently catalyze reversible interconversion of a low-active precursor estrogen estrone (E1) to the highly active E2 that is necessary for normal ovary development [ 13 , 45 ]. It is the major isozyme in the granulosa cells of the ovary and has a central role in regulating the circulating estradiol concentration as well as its local production in estrogen target cells, locally promotes development, differentiation, and maturation of the follicle [ 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a plethora of ovarian paracrine and autocrine factors was involved in regulation of the follicle development and its function as well as the positive or negative controls through the endocrinal hormones from the hypothalamus and pituitary, including gonadotropin releasing hormone (GNRH), gonadotropin inhibitory hormone (GNIH), and follicle stimulating hormone (FSH) [ 1 , 2 , 8 ]. Within the ovary, the most representative hormones and growth factors such as steroidogenic-related enzymes steroidogenic acute regulatory protein (STAR), hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) and cytochrome P450 side-chain cleavage (P450scc/CYP11A1), intra-ovarian hormones progesterone (P4), estradiol (E2) and anti-müllerian hormone (AMH), cell proliferation or apoptosis-related factors Bcl-2, cyclin D1 (CCND1) and caspase-3 (CASP3), which have indispensable effects on follicular development, follicle selection or atresia, finally on their preovulatory development and ovulation, making the early developmental differences of ovarian follicles and egg production capacity in adult layers highly correlated, have been intensively investigated [ 9 – 13 ]. Undoubtedly, follicular size has a close relationship with its developmental biology, physiological function, and molecular regulation.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production

et al. 2021

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Background Ovarian follicle development plays an important role in determination of poultry egg production. The follicles at the various developmental stages possess their own distinct molecular genetic characteristics and have different biological roles in chicken ovary development and function. In the each stage, several genes of follicle-specific expression and biological pathways are involved in the vary-sized follicular development and physiological events. Identification of the pivotal genes and signaling pathways that control the follicular development is helpful for understanding their exact regulatory functions and molecular mechanisms underlying egg-laying traits of laying hens. Results The comparative mRNA transcriptomic analysis of ovarian follicles at three key developmental stages including slow growing white follicles (GWF), small yellow follicles (SYF) of recruitment into the hierarchy, and differentiated large yellow follicles (LYF), was accomplished in the layers with lower and higher egg production. Totally, 137, 447, and 229 of up-regulated differentially expressed genes (DEGs), and 99, 97, and 157 of down-regulated DEGs in the GWF, SYF and LYF follicles, including VIPR1, VIPR2, ADRB2, and HSD17B1 were identified, respectively. Moreover, NDUFAB1 and GABRA1 genes, two most promising candidates potentially associated with egg-laying performance were screened out from the 13 co-expressed DEGs in the GWF, SYF and LYF samples. We further investigated the biological effects of NDUFAB1 and GABRA1 on ovarian follicular development and found that NDUFAB1 promotes follicle development by stimulating granulosa cell (GC) proliferation and decreasing cell apoptosis, increases the expression of CCND1 and BCL-2 but attenuates the expression of caspase-3, and facilitates steroidogenesis by enhancing the expression of STAR and CYP11A1. In contrast, GABRA1 inhibits GC proliferation and stimulates cell apoptosis, decreases the expression of CCND1, BCL-2, STAR, and CYP11A1 but elevates the expression of caspase-3. Furthermore, the three crucial signaling pathways such as PPAR signaling pathway, cAMP signaling pathway and neuroactive ligand-receptor interaction were significantly enriched, which may play essential roles in ovarian follicle growth, differentiation, follicle selection, and maturation. Conclusions The current study provided new molecular data for insight into the regulatory mechanism underlying ovarian follicle development associated with egg production in chicken.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production

et al. 2021

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“…HSD17B1 contains 327 amino acids, with a subunit mass of 34.8 kDa, and is highly expressed in the placenta and ovaries. [ 31 ] In addition, HSD17B1 has an N‐terminal short‐chain dehydrogenase domain and a narrow hydrophobic C‐terminal domain that bind with a cofactor and steroid substrate, respectively. [ 32 ] We are currently noting an increasing number of studies on HSD17B1 inhibitors for the treatment of hormone‐dependent diseases, including endometriosis, breast cancers, and cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1

Cheng

Shen

Ding

et al. 2020

Molecular Nutrition Food Res

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Scope: Maca (Lepidium meyenii), a well-known plant from the Andean highlands of Peru, has been used widely as a nutritional supplement to increase sexual function and fecundity. However, the identity of its active ingredients and how they function remain unknown. Methods and results: Chemical substances in maca are identified by UPLC-Q-TOF, and the active ingredients are screened through HotMap coupled with an artificial neural network. Lepidiline A (LA), an imidazole alkaloid, is identified as the key active compound. LA affects the balance of endogenous sex hormones in mice and improves fecundity in Drosophila. Using a molecular LA probe, 17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) is revealed to be the potential target of LA using a fishing-rod strategy. It is demonstrated with experimental data that LA targets HSD17B1 to enhance the enzyme's activity and increases its bioconversion efficiency of actively formed sex hormones including estrogen to 17 -estradiol and 4-androsten-3,7-dione to testosterone, which ultimately improves reproductive activity. Conclusion: LA improves the balance of endogenous sex hormones and increases fecundity by targeting HSD17B1. This underlying mechanism of action provides a useful insight into the application of maca in the regulation of dietary nutrition and healthy fertility.

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“…Due to their side effect profile, European (ESHRE) guidelines recommend they are used in combination with other drugs and not as a first line therapy (Dunselman et al, 2014). New Review generations of drugs that target other enzymes overexpressed in endometriosis lesions include those directed at 17betaHSD1 (Heinosalo et al, 2019), dual inhibitors of steroid sulfatase/17be-taHSD (Salah et al, 2017(Salah et al, , 2019, and AKR1C3 (Ri zner and Penning, 2020). Although a clinical trial for the 17ßHSD inhibitor FOR-6219 is underway (Table 3), trials with the AKR1C3 inhibitor BAY1128688 were terminated early due to reports of hepatotoxicity (NCT03373422).…”

Section: Llmentioning

confidence: 99%

Endometriosis: Etiology, pathobiology, and therapeutic prospects

Saunders

Horne

2021

Cell

390

389

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Role of hydroxysteroid (17beta) dehydrogenase type 1 in reproductive tissues and hormone-dependent diseases

Cited by 18 publications

References 256 publications

Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production

Transcriptome comparative analysis of ovarian follicles reveals the key genes and signaling pathways implicated in hen egg production

Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1

Endometriosis: Etiology, pathobiology, and therapeutic prospects

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