adrb2 antagonist zenidolol  (MedChemExpress)

Journal: Advanced Science

Article Title: Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via β2 Adrenergic Receptor Signaling

doi: 10.1002/advs.202402393

Figure Lengend Snippet: Activation of the ADRB2 signaling pathway induces the loss of primordial follicles. A) Significant reduction in ovarian weight in mice after administering water containing ADRB2 agonist CLEN for 6 days (CON n = 22, CLEN n = 22). Statistical method: Mann‐Whitney test. B) Number of primordial follicles, antral follicles, and total follicle count in mice after treatment with ADRB2 agonist CLEN (CON n = 5, CLEN n = 5). Statistical method: Independent Samples Test. C) Significant reduction in ovarian weight in mice after intraperitoneal administration of another ADRB2 agonist SAL for 6 days (CON n = 12, SAL n = 12). Statistical method: Independent Samples Test. D) Number of primordial follicles, antral follicles and total follicle count in mice after treatment with ADRB2 agonist SAL (CON n = 5, SAL n = 5). Statistical method: Independent Samples Test. E) ADRB2 antagonist ICI was intraperitoneally injected to rescue SD mice, showing significant recovery of ovarian weight in mice after addition of ICI to SD6D mice (CON n = 12, SD6D n = 12, SD6D + ICI n = 12, ICI n = 12). Statistical method: Independent‐Samples Kruskal‐Wallis Test. F) Number of primordial follicles, antral follicles and total follicle count in mice after treatment with ADRB2 antagonist ICI (CON n = 5, SD6D n = 5, SD6D + ICI n = 5, ICI n = 5). Statistical methods: Primordial follicles: Independent‐Samples Kruskal‐Wallis Test; Antral follicles: One‐way ANOVA with LSD Test; Total follicles: Independent‐Samples Kruskal‐Wallis Test. Data are presented as mean with SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, and ns indicates not significant. CON, control; SD, sleep deprivation; CLEN, Clenbuterol; SAL, Salbutamol; ICI, ICI‐118551.

Article Snippet: The ADRB2 antagonist ICI (MCE, HY‐13951), dissolved in DMSO, was administered via daily intraperitoneal injections (5 mg kg −1 ) for 6 days.

Techniques: Activation Assay, MANN-WHITNEY, Injection, Control

Journal: Advanced Science

Article Title: Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via β2 Adrenergic Receptor Signaling

doi: 10.1002/advs.202402393

Figure Lengend Snippet: Activated ADRB2 upregulates KITL via the cAMP/PKA pathway. A) After treating mice with the ADRB2 agonist CLEN, Western blot analysis revealed high expression of KIT/KITL in ovarian tissue (KIT: CON n = 3, CLEN n = 4), (KITL: CON n = 5, CLEN n = 6). Statistical methods: KIT: Independent Samples Test; KITL: Mann‐Whitney Test. B) Similarly, after treatment with another ADRB2 agonist SAL, Western blot analysis showed high expression of KIT/ KITL in ovarian tissue (CON n = 3, SAL n = 3). Statistical methods: KIT: Independent Samples Test; KITL: Mann‐Whitney Test. C) Stimulation of the human granulosa cell line KGN with CLEN and SAL at a concentration of 1 and 100 µ m , respectively, resulted in a significant upregulation of KITL mRNA expression (CON n = 3, CLEN n = 3) (CON n = 3, SAL n = 3). Statistical method: Independent Samples Test. D,E) Following treatment with CLEN and SAL, Western blot analysis revealed a significant increase in KITL protein levels in KGN cells (CON n = 5, CLEN n = 4) (CON n = 4, SAL n = 4). Statistical method: Independent Samples Test. F) After treatment with CLEN and SAL, KGN cells were collected and subjected to cAMP ELISA testing, which showed a significant increase in cellular cAMP content compared to control cells (CON n = 4, CLEN n = 4; SAL n = 4). Statistical method: One‐way ANOVA with LSD Test. G,H) Following treatment with CLEN and SAL, Western blot analysis showed a significant upregulation of p‐PKA levels in KGN cells (CON n = 3, CLEN n = 3) (CON n = 4, SAL n = 4). Statistical method: Independent Samples Test. I) Correlation analysis of the protein levels of KITL and p‐PKA in KGN cells revealed a strong correlation between the expression levels of these two proteins, with a Pearson correlation of 0.925 ( n = 8, p = 0.001**). J) After treating KGN cells with 20 µ m of cAMP, the expression level of KITL significantly increased (CON n = 4, cAMP n = 4). Statistical method: Mann‐Whitney Test. K) Treatment of KGN cells with 10 n m concentration of the PKA activator BC resulted in a significant upregulation of KITL levels (CON n = 4, BC n = 5). Statistical method: Independent Samples Test. L,M) Treatment of KGN with the PKA antagonists STA and H89 in a 100 n m concentration led to a significant downregulation of KITL levels (CON n = 5, STA n = 4) (CON n = 5, H89 n = 4). Statistical method: Independent Samples Test. Data are presented as mean with SEM. In all panels, * p < 0.05, ** p < 0.01, and *** p < 0.001. CON, control; CLEN, Clenbuterol; SAL, Salbutamol; BC, Bucladesine sodium; STA, Staurosporine; H89, H‐89 dihydrochloride; KITL, KIT ligand.

Article Snippet: The ADRB2 antagonist ICI (MCE, HY‐13951), dissolved in DMSO, was administered via daily intraperitoneal injections (5 mg kg −1 ) for 6 days.

Techniques: Western Blot, Expressing, MANN-WHITNEY, Concentration Assay, Enzyme-linked Immunosorbent Assay, Control

Journal: Advanced Science

Article Title: Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via β2 Adrenergic Receptor Signaling

doi: 10.1002/advs.202402393

Figure Lengend Snippet: A schematic model depicting the mechanism of activation of ovarian primordial follicles induced by SD. SD leads to adrenal hyperactivity, resulting in the secretion of NE and E, which act on the ADRB2 of granulosa cells in primordial follicles of the ovary. This activation of ADRB2 triggers the cAMP/PKA and cAMP/mTOR signaling pathway in granulosa cells, leading to increased expression of KITL which initiating the activating of primordial follicles. Overactivation of primordial follicles accelerates the depletion of ovarian reserves and ultimately reduces the reproductive longevity. SD, sleep deprivation; NE, norepinephrine; E, epinephrine; ADRB2, β2‐adrenergic receptor.

Article Snippet: The ADRB2 antagonist ICI (MCE, HY‐13951), dissolved in DMSO, was administered via daily intraperitoneal injections (5 mg kg −1 ) for 6 days.

Techniques: Activation Assay, Expressing