FSH
目录号 : GP21245FSH 是窦状卵泡的主要存活因子，已被认为可以提高 GC 对卵泡闭锁期间氧化应激的抵抗力。
Sample solution is provided at 25 µL, 10mM.
| Cell experiment [1]: | |
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Cell lines |
Ovarian granulosa cells (GCs) |
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Preparation Method |
GCs transfected with GFP-MAP1LC3B plasmid for 48 h were incubated with 200 µM H2O2 for 1 h and cultured for another 2 h in the presence or absence of FSH (7.5 IU/ml), pepstatin A and E64. |
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Reaction Conditions |
FSH (7.5 IU/ml) for 2 h |
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Applications |
FSH reduces oxidative injury in cultured GCs via inhibiting autophagic PCD. |
| Animal experiment [2]: | |
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Animal models |
Cebpb+/ 3xTg mutant mice |
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Preparation Method |
I.p. injected 2.5- to 3-month-old compound mutant mice with FSH (5 IU per mouse) daily for 3 months |
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Dosage form |
5 IU FSH for 3 months |
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Applications |
FSH-induced Cebpb, Lgmn, App and Mapt expression, AEP activation, APP and Tau cleavage, Aβ and pTau accumulation, dendritic spine deficits and cognition defects were all lower in Cebpb+/ 3xTg mice compared with 3xTg mice. |
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References: [1].Shen M, Jiang Y, et,al.Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy. Autophagy. 2017 Aug 3;13(8):1364-1385. doi: 10.1080/15548627.2017.1327941. Epub 2017 Jun 9. PMID: 28598230; PMCID: PMC5584866. |
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FSH, a major survival factor for antral follicles, has been suggested to improve GC resistance to oxidative stress during follicular atresia[2].
The decline in GCs viability caused by oxidant injury was remarkably reduced following FSH treatment, along with impaired macroautophagic/autophagic flux under conditions of oxidative stress both in vivo and in vitro. Blocking of autophagy displayed similar levels of suppression in oxidant-induced cell death compared with FSH treatment, but FSH did not further improve survival of GCs pretreated with autophagy inhibitors. FSH inhibited the production of acetylated FOXO1 and its interaction with Atg proteins, followed by a decreased level of autophagic cell death upon oxidative stress[1]. FSH dampened stress-induced apoptosis and the expression of FoxO1 and pro-apoptosis genes in mouse granulosa cells (MGCs). The signaling cascades involved in regulating FoxO1 activity upon FSH treatment were identified using FSH signaling antagonists[3].
FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer's disease. Blocking FSH action in these mice abrogates the Alzheimer's disease-like phenotype by inhibiting the neuronal C/EBPβ-δ-secretase pathway[4]. FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator[6]. When generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model[5]. FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility[7].
References:
[1]. Shen M, Jiang Y, et,al.. Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy. Autophagy. 2017 Aug 3;13(8):1364-1385. doi: 10.1080/15548627.2017.1327941. Epub 2017 Jun 9. PMID: 28598230; PMCID: PMC5584866.
[2]. Peluso JJ, Steger RW. Role of FSH in regulating granulosa cell division and follicular atresia in rats. J Reprod Fertil. 1978 Nov;54(2):275-8. doi: 10.1530/jrf.0.0540275. PMID: 722676.
[3]. Shen M, Liu Z, et,al. Involvement of FoxO1 in the effects of follicle-stimulating hormone on inhibition of apoptosis in mouse granulosa cells. Cell Death Dis. 2014 Oct 16;5(10):e1475. doi: 10.1038/cddis.2014.400. PMID: 25321482; PMCID: PMC4237239.
[4]. Xiong J, Kang SS, et,al. FSH blockade improves cognition in mice with Alzheimer's disease. Nature. 2022 Mar;603(7901):470-476. doi: 10.1038/s41586-022-04463-0. Epub 2022 Mar 2. PMID: 35236988.
[5]. Guo Y, Zhao M, et,al.Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol. Cell Res. 2019 Feb;29(2):151-166. doi: 10.1038/s41422-018-0123-6. Epub 2018 Dec 17. PMID: 30559440; PMCID: PMC6355920.
[6]. Zhang M, Wang Y, et,al. FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway. J Bone Miner Metab. 2021 Sep;39(5):769-779. doi: 10.1007/s00774-021-01232-3. Epub 2021 May 14. PMID: 33988757.
[7]. Walters KA, Edwards MC, et,al. Subfertility in androgen-insensitive female mice is rescued by transgenic FSH. Reprod Fertil Dev. 2017 Jul;29(7):1426-1434. doi: 10.1071/RD16022. PMID: 27328025.
| Purity | Source | Urine of post-menopausal women. | |
| Phycical Appearance | Sterile Filtered White lyophilized (freeze-dried) powder. | Shipping Condition | Shipped at Room temp. |
| Synonyms | Follitropin subunit beta; Follicle-stimulating hormone beta subunit; FSH-beta; FSH-B; Follitropin beta chain; FSH. | ||
| Solubility | It is recommended to reconstitute the lyophilized Follicle Stimulating Hormone in sterile pyrogen free water at 100IU/0.1ml, which can then be further diluted to other aqueous solutions. | ||
| Stability | Lyophilized FSH although stable at room temperature for 3 weeks, should be stored desiccated below -18°C . Upon reconstitution FSH-beta should be stored at 4°C between 2-7 days and for future use below -18°C . For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA).Please prevent freeze-thaw cycles. | ||
| Formulation | The FSH was lyophilized with no additives. | ||
Follicle stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland. FSH and LH act synergistically in reproductionIn women, in the ovary FSH stimulates the growth of immature Graafian follicles to maturation. As the follicle grows it releases inhibin, which shuts off the FSH production. In men, FSH enhances the production of androgen-binding proteinby the Sertoli cells of the testes and is critical for spermatogenesis. In both males and females, FSH stimulates the maturation of germ cells. In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the concomitant rise in inhibin B FSH levels then decline in the late follicular phase. This seems to be critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal phase, there is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle.Like its partner, LH, FSH release at the pituitary gland is controlled by pulses of gonadotropin-releasing hormone(GnRH). Those pulses, in turn, are subject to the estrogen feed-back from the gonads.
Lyophilized FSH although stable at room temperature for 3 weeks, should be stored desiccated below -18°C . Upon reconstitution FSH-beta should be stored at 4°C between 2-7 days and for future use below -18°C . For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA).Please prevent freeze-thaw cycles.
Interactions between androgens, FSH, anti-M¨¹llerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary
Hum Reprod Update2016 Nov;22(6):709-724.PMID: 27566840DOI: 10.1093/humupd/dmw027
Background: Androgens, FSH, anti-M¨¹llerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. Objectives and rationale: The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). Search methods: A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science. Outcomes: During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the abnormally persisting inhibition of FSH effects by AMH that blocks aromatase. Beside anovulation, this scenario may also serve to explain the higher receptiveness to gonadotropin therapy and the increased risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS. Wider implications: Within GCs, the balance between FSH and AMH effects is pivotal in the shift from androgen- to oestrogen-driven follicles. Our two triangles hypothesis, based on updated data from the literature, offers a pedagogic template for the understanding of folliculogenesis in the normal and polycystic ovary. It opens new avenues for the treatment of anovulation due to PCOS.
An FSH booster surge for resurgence of the preovulatory follicle in heifers
Domest Anim Endocrinol2018 Oct;65:90-94.PMID: 30032022DOI: 10.1016/j.domaniend.2018.06.002
Emergence of wave 1 during an interovulatory interval (IOI) in heifers is stimulated by FSH surge 1. A minor FSH surge with absence of a dominant follicle in the associated follicular wave occurs immediately before FSH surge 1. This minor surge is termed an FSH booster surge owing to its occurrence temporally during a resurgence of a preovulatory follicle that has been decreasing or lagging in growth rate for several days. The beginning nadir, peak, and ending nadir of the FSH booster surge occur at means of 7, 4, and 3 d before ovulation. The beginning nadir occurs at the beginning of a decrease in growth rate of the preovulatory follicle, and the peak occurs at the beginning of resurgence. The frequency of an FSH booster surge in 1 study was 10/17 (59%) and 4/18 (22%) in 2-wave and 3-wave IOI, respectively. The presence versus absence of a booster surge in 3-wave IOI is associated with a slower growth rate of the preovulatory follicle and a longer IOI. Most 3-wave IOI have rapid growth rate of the preovulatory follicle and do not have an FSH booster surge. Estradiol is a known FSH suppressor and begins to decrease at the beginning of the FSH booster surge and the beginning of a lag in growth rate of the preovulatory follicle. Concentration of LH increases significantly by the day of the peak of the booster surge. However, LH increases during waves with and without resurgence of the preovulatory follicle, whereas the FSH booster surge develops only in waves with resurgence in both 2-wave and 3-wave IOI. The beginning nadir of the booster surge is accompanied sometimes (eg, 6 of 10 surges) by the emergence of a minor follicular wave which does not develop a dominant follicle. Emergence of the booster wave and beginning FSH nadir occur earlier than the first progressive increase in LH indicating that the minor wave is attributable to the FSH booster surge. Based on temporality, the booster surge is used to stimulate recruitment or emergence of some of the small antral follicles (eg, 1 and 2 mm) that will become part of wave 1 of the next IOI. The primary function of the FSH booster surge as indicated by close temporality is to stimulate resurgence of a preovulatory follicle that has been lagging in growth rate. It is not known whether the booster surge and resurgence of the preovulatory follicle are essential for complete and normal maturation of the follicle and oocyte and for ovulation.
Estrogen Versus FSH Effects on Bone Metabolism: Evidence From Interventional Human Studies
Endocrinology2020 Aug 1;161(8):bqaa111.PMID: 32602895DOI: 10.1210/endocr/bqaa111
Provocative mouse studies and observational human data have generated considerable enthusiasm for modulating follicle-stimulating hormone (FSH) action in humans to prevent bone loss and, in addition, to treat obesity. This perspective summarizes the strengths and potential weaknesses of the mouse studies examining the skeletal phenotype of FSH¦ or FSH receptor null mice, as well as more recent studies using FSH neutralizing antibodies. Although human observational studies do demonstrate correlation of serum FSH levels with postmenopausal bone loss, these studies cannot distinguish whether serum FSH is simply a better biomarker than estradiol or causally related to the bone loss. Establishing causality requires direct interventional studies either suppressing or infusing FSH in humans and to date, such studies have uniformly failed to demonstrate an effect of FSH on bone turnover independent of changes in sex steroid levels. In addition, suppression of FSH is unable to prevent increases in body fat following the induction of sex steroid deficiency, at least in men. Thus, although the preclinical mouse and human observational data are intriguing, there is currently no direct evidence from interventional studies that FSH regulates bone or fat metabolism in vivo in humans.
FSH directly regulates chondrocyte dedifferentiation and cartilage development
J Endocrinol2021 Feb;248(2):193-206.PMID: 33295881DOI: 10.1530/JOE-20-0390
Previous studies suggest that postmenopausal osteoarthritis is linked to a decrease in estrogen levels. However, whether follicle-stimulating hormone (FSH), the upstream hormone of estrogen, affects cartilage destruction and thus contributes to the onset of osteoarthritis has never been explored. To evaluate the potential involvement of FSH in joint degeneration and to identify the molecular mechanisms through which FSH influences chondrocytes, mouse cartilage chondrocytes and the ATDC5 chondrocyte cell line were treated with FSH and inhibitors of intracellular signaling pathways. We observed that FSH induces chondrocyte dedifferentiation by decreasing type II collagen (Coll-II) synthesis. Chondrocyte cytoskeleton reorganization was also observed after FSH treatment. The FSH-induced decrease in Coll-II was rescued by ERK-1/2 inhibition but aggravated by p38 inhibition. In addition, knocking down the FSH receptor (Fshr) by using Fshr siRNA abolished chondrocyte dedifferentiation, as indicated by the increased expression of Coll-II. Inhibition of the protein G¦Ái by pertussis toxin (PTX) also restored FSH-inhibited Coll-II, suggesting that G¦Ái is downstream of FSHR in chondrocyte dedifferentiation. FSH¦ antibody blockade prevented cartilage destruction and cell loss in mice. Moreover, decreased Coll-II staining due to the progression of aging could be rescued by blocking FSH. Thus, we suggest that high circulating FSH, independent of estrogen, is an important regulator in chondrocyte dedifferentiation and cartilage destruction.
Extragonadal Actions of FSH: A Critical Need for Novel Genetic Models
Endocrinology2018 Jan 1;159(1):2-8.PMID: 29236987DOI: 10.1210/en.2017-03118
Follicle-stimulating hormone (FSH) is critical for ovarian folliculogenesis and essential for female fertility. FSH binds to FSH receptors (FSHRs) and regulates estrogen production in ovarian granulosa cells to orchestrate female reproductive physiology. Ovarian senescence that occurs as a function of aging results in loss of estrogen production, and this is believed to be the major reason for bone loss in postmenopausal women. Although conflicting, studies in rodents and humans during the last decade have provided genetic, pharmacological, and physiological evidence that elevated FSH levels that occur in the face of normal or declining estrogen levels directly regulate bone mass and adiposity. Recently, an efficacious blocking polyclonal FSH¦ antibody was developed that inhibited ovariectomy-induced bone loss and triggered white-to-brown fat conversion accompanied by mitochondrial biogenesis in mice. Moreover, additional nongonadal targets of FSH action have been identified, and these include the female reproductive tract (endometrium and myometrium), the placenta, hepatocytes, and blood vessels. In this mini-review, I summarize these studies in mice and humans and discuss critical gaps in our knowledge, yet unanswered questions, and the rationale for developing novel genetic models to unambiguously address the extragonadal actions of FSH.