The adrenergic receptor beta2 is a subtype of adrenergic receptors, all of them with seven transmembrane regions, coupled to G proteins. The beta 2 subtype is preferentially coupled to the Gs protein, leading to an increase in cAMP production.
NCBI Summary:
This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Steroid metabolism, Luteinization
Comment
Adashi et al. (1981) demonstrated the presence of functional beta2-adrenergic receptor in rat granulosa cells. Hernandez et al. (1988) reported that adrenergic regulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic theca-interstitial cell recognition sites. Luck et al. (1991) reported that beta adrenoceptors mediate the catecholamine-induced stimulation of oxytocin secretion from cultured bovine granulosa cells.
The influence of alpha-adrenergic receptors stimulator and blockers and beta-blocker on the ovary and endocrinological activity in heifers during superovulation. Gajewski Z et al. Twenty five Holstein-Friesian heifers, clinically normal and with regular oestrous cycles, were used for induction of superovulation (PMSG-PGF(2)alpha-Neutra-PMSG). Animals were divided into 5 groups receiving: I - detomidine (40 mug/kg b.w.), II - doxazosin (0.2 mg/kg b.w.), III - yohimbine HCL 1% (1 ml/50 kg b.w.), IV - carazolol (0.01 mg/ kg b.w., i.v.), and V - physiological saline (1 ml/50 kg b.w.). The heifers with PGF2alpha-induced cycles were treated with the substances 88 hrs after being given a single i.m. injection of 2500 IU PMSG. All animals were examined by ultrasonography, and by the number and size of ovarian follicles > 3 mm in diameter. The follicles were divided into 3 groups according to the diameter. Blood plasma was stored at -20 degrees C until LH, P4, E2 and PGFM analyses. In the control (V) group, two waves of follicle growth were observed. Yohimbine produced a significant blockage of ovulation. The mean number of corpora lutea in the group III was significantly lower than that in the control group (p< 0.02). No significant differences in the number of corpora lutea were observed between the groups I, II and III. The increase in E2 concentrations could be the response to the PMSG treatment with two waves of growth of large follicles before and after ovulation. Pulsatile LH release was altered by yohimbinum injection, however, the greater amplitude of pulses immediately following yohimbinum administration are suggestive of a positive influence of the alpha-2 adrenergic receptors antagonist. Yohimbinum administration did not affect plasma concentration of examined hormones. There was a difference between the plasma levels of LH after the doxazosin injection. Single injection of the stimulators and blockers of adrenergic receptors did not affect superovulatory response in terms of the numbers of CL, unruptured follicles and embryos recovered. The affectivity of artificial insemination was not significantly different between the control group and the detomidinum groups, while in the yohimbinum group it was significantly lower.
Expression regulated by
FSH
Comment
Adashi et al. (1981) demonstrated the stimulation of beta 2-adrenergic responsiveness by follicle-stimulating hormone in rat granulosa cells in vitro and in vivo. The results suggest that FSH treatment in vivo and in vitro increases beta 2-adrenergic responsiveness in ovarian granulosa cells and that this functional responsiveness is coupled to progesterone, but not to estrogen, biosynthesis.
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Expression of the beta-2 adrenergic receptor (ADRB-2) in human and monkey ovarian follicles: a marker of growing follicles? Merz C et al. (2015) ADRB-2 was implicated in rodent ovarian functions, including initial follicular growth. In contrast, ADRB-2 expression and function in nonhuman primate and human ovary were not fully known but innervation and significant levels of norepinephrine (NE), which is a ligand at the ADRB-2, were reported in the ovary. We studied expression of ADRB-2 in human and rhesus monkey ovary (RT-PCR, immunohistochemistry; laser micro dissection) and measured levels of norepinephrine (NE; ELISA) in monkey follicular fluid (FF). 3D cultures of monkey follicles (4 animals) were exposed to NE or the ADRB-2 agonist isoproterenol (ISO), and follicular development (size) was monitored. Upon termination expression of ADRB-2, FSH receptor and aromatase genes were examined. Immunohistochemistry and RT-PCR of either human follicular granulosa cells (GCs) obtained by laser micro dissection or isolated monkey follicles revealed ADRB-2 in GCs of primordial, primary, secondary and tertiary follicles. Staining of GCs in primordial and primary follicles was intense. In large preantral and antral follicles the staining was heterogeneous, with positive and negative GCs present but GCs lining the antrum of large follicles were generally strongly immunopositive. Theca, interstitial, and ovarian surface epithelial cells were also positive. NE was detected in FF of preovulatory antral monkey follicles (0.37 + 0.05 ng/ml; n = 7; ELISA) but not in serum. We examined preantral follicles ranging from 152 to 366 μm in diameter in a 3D culture in media supplemented with follicle stimulating hormone (FSH). Under these conditions, neither NE, nor ISO, influenced growth rate in a period lasting up to one month. Upon termination of the cultures, all surviving follicles expressed aromatase and FSH receptors, but only about half of them also co-expressed ADRB-2. The ADRB-2 expression was not correlated with the treatment but was positively correlated with the follicular size at the beginning and at the end of the culture period. Hence, expression of ADRB-2 was found in the largest and fastest-in vitro growing follicles. The results imply ADRB-2-mediated actions in the development of primate follicles. Drugs interfering with ADRB-2 are used to treat medical conditions and may have unexplored effects in the human ovary.//////////////////
Norjavaara et al. (1984) have measured the beta-adrenergic receptor content in rat corpora lutea. The rat luteal beta-adrenergic receptor seems to be of the beta 2-subtype as determined from adenylate cyclase stimulation as well as from displacement of [125I]iodo-HYP binding by various beta-adrenergic agonists.
Follicle stages
Primary, Secondary, Antral, Preovulatory, Corpus luteum
Comment
Aguado et al. (1984) suggested that during prepubertal maturation, noradrenergic fibers reaching the ovary via the supraoptic nuclei may modify ovarian steridogenic sensitivity to catecholamines by regulating the number of functional beta-adrenergic receptors in the gland.
alpha(2beta) adrenoreceptor 301-303 deletion polymorphism in polycystic ovary syndrome. Saltamavros AD et al. alpha(2beta) adrenoreceptor 301-303 deletion polymorphism does not influence basal metabolic rate, insulin resistance or weight gain in Greek women with polycystic ovary syndrome.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: Association between ?-adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS. Tellechea ML et al. OBJETIVE: The aim of this study was to explore ?-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. DESIGN: Genetic polymorphism analysis. Cross sectional case-control association study. SETTING: Medical?University Hospital and research laboratory. PATIENTS: 165 unrelated women with PCOS and 116 unrelated women without PCOS (control sample). MEASUREMENTS: Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. The aim of this study was to explore ?-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic METHODS: ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. RESULTS: We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (p=0.018) and HOMA (p=0.008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (p=0.043), taking into account confounding variables. CONCLUSIONS: Haplotype I (CCGG) has a protective role for IR and MS in PCOS. ? 2012 Blackwell Publishing Ltd.