Estrogen receptor profiles across tissues from male and female Rattus norvegicus

Abstract

BackgroundEstrogen is formed by the enzyme aromatase (CYP19A1) and signals via three identified receptors ERα (ESR1), ERß (ESR2), and the G protein-coupled estrogen receptor (GPER). Understanding the relative contribution of each receptor to estrogenic signaling may elucidate the disparate effects of this sex hormone across tissues, and recent developments in PCR technology allow absolute quantification and direct comparison of multiple targets. We hypothesized that this approach would reveal tissue- and sex-specific differences in estrogen receptor mRNA.MethodsESR1, ESR2, GPER, and CYP19A1 were measured in four cardiovascular tissues (heart, aorta, kidney, and adrenal gland), three brain areas (somatosensory cortex, hippocampus, and prefrontal cortex), and reproductive tissues (ovaries, mammary gland, uterus, testes) from six male and six female adult Sprague-Dawley rats.ResultsGPER mRNA expression was relatively stable across all tissues in both sexes, ranging from 5.49 to 113 copies/ng RNA, a 21-fold difference. In contrast, ESR1/ESR2 were variable across tissues although similar within an organ system. ESR1 ranged from 4.46 to 614 copies/ng RNA (138-fold difference) while ESR2 ranged from 0.154 to 83.1 copies/ng RNA (540-fold). Significant sex differences were broadly absent except for renal ESR1 (female 206 vs. male 614 copies/ng RNA, P < 0.0001) and GPER (62.0 vs. 30.2 copies/ng RNA, P < 0.05) as well as gonadal GPER (5.49 vs. 47.5 copies/ng RNA, P < 0.01), ESR2 (83.1 vs. 0.299 copies/ng RNA, P < 0.01), and CYP19A1 (322 vs. 7.18 copies/ng RNA, P < 0.01). Cardiovascular tissues showed a predominance of ESR1, followed by GPER. In contrast, GPER was the predominant transcript in the brain with similarly low levels of ESR1 and ESR2. CYP19A1 was detected at very low levels except for reproductive tissues and the hippocampus.ConclusionWhile the data indicates a lack of sex differences in most tissues, significant differences were found in the range of receptor gene expression across tissues as well as in the receptor profile between organ systems. The data provide a guide for future studies by establishing estrogen receptor expression across multiple tissues using absolute PCR quantification. This knowledge on tissue-specific estrogen receptor profiles will aid the development of hormonal therapies that elicit beneficial effects in specific tissues.

Role for ovarian hormones in purinoceptor-dependent natriuresis

“…regulates the renal medullary P2 system. Notably, renal estrogen receptor, ER, expression has been shown in multiple studies [36][37][38]. Binding studies using radiolabeled E2 revealed that radioactivity localizes to the proximal tubule and the inner medullary collecting duct [39], which is relevant to our findings in mIMCD3 cells.…”

G protein‐coupled oestrogen receptor stimulation ameliorates iron‐ and ovariectomy‐induced memory impairments through the cAMP/PKA/CREB signalling pathway

“…Thus, considering that a single post‐training administration of G1 was able to restore memory in both iron‐ and iron‐OVX rats, we can propose that the stimulation of GPER contributes to memory consolidation by ameliorating memory deficits. In addition, a very recent study reported that GPER is highly expressed in brain areas such as the somatosensory and prefrontal cortex in both sexes, with its expression in these areas being higher than classical oestrogen receptors ERα and ERβ . Because G1 was administered systemically, its positive effects on cognition may be related to GEPR stimulation in other brain areas implicated in memory consolidation such as the prefrontal cortex.…”

“…In addition, a very recent study reported that GPER is highly expressed in brain areas such as the somatosensory and prefrontal cortex in both sexes, with its expression in these areas being higher than classical oestrogen receptors ERα and ERβ. 45 Because G1 was administered systemically, its positive effects on cognition may be related to GEPR stimulation in other brain areas implicated in memory consolidation such as the prefrontal cortex.…”

Female Heart Health: Is GPER the Missing Link?

“…ERα and GPER are expressed at similar levels in cardiac tissue from male and female rodents (46) as well as from humans (47). In contrast, reports of ERβ expression in the heart are conflicting, with ERβ mRNA detected in human cardiac tissue (48) but remaining below detectable levels in rodent cardiac tissue (46,49). Based on observed improvement in cardiac function in response to E 2 treatment in postmenopausal women (50) and in ovariectomized (OVX) rats (21), researchers have attempted to identify the primary receptor mediating estrogen's cardioprotective effects.…”

“…G15 and G36 are antagonists of GPER with low affinity binding to the classical estrogen receptors (64). While the exact signaling actions and transduction pathways of cardiac GPER are not completely understood, they are likely dependent on the cell type, site of action and the relative levels in comparison with the other estrogen receptors (46). The selective GPER agonist G1 modulates fast transduction pathways in the heart that are involved in (1) controlling intracellular calcium via actions on cardiac channels and pumps, (2) regulating phosphoinositide 3kinase (PI3Ks) and extracellular signal-related kinases (ERKs), and (3) modulating cyclic adenosine monophosphate (cAMP) (see sections Effects of Estrogen and GPER Activation on I Ca,L and Estrogen, GPER, and SERCA2a and Its Regulatory Proteins below).…”