Objective The aim of the study was to determine the association of urinary levels of estradiol(E_(2))and 2-methoxyestradiol(2-MeOE_(2))with the occurrence and development of endometrial cancer.Methods In this case-con...Objective The aim of the study was to determine the association of urinary levels of estradiol(E_(2))and 2-methoxyestradiol(2-MeOE_(2))with the occurrence and development of endometrial cancer.Methods In this case-control study,24-h urine specimens were collected from 28 postmenopausal patients with endometrial cancer and 28 postmenopausal healthy female controls.The concentration of 2-MeOE_(2) was determined using liquid chromatography-mass spectrometry with hollow fiber liquid-phase microextraction.The concentration of E_(2) was determined using an enzyme-linked immunosorbent assay.Results Estrogen levels were different between the patients with endometrial cancer and controls.The relative quantity of E_(2) in the case group was higher than that in the control group(P<0.05),whereas that of 2-MeOE_(2) was lower in the case group than that in the control group(P<0.05).The ratio of E_(2)-to-2-MeOE_(2) in the case group was significantly higher than that in the control group(P<0.05).Conclusion The results of this study indicate an imbalance of estrogen metabolites in endometrial carcinogenesis.Reduced 2-MeOE_(2) levels and elevated E_(2)-to-2-MeOE_(2) ratio may be used as potential biomarkers for the risk assessment of estrogen-induced endometrial cancer.展开更多
Background： Estradiol （E2） is required for luteolysis in cows and its injection stimulates prostaglandin F2α （PGF2α） release. The main goal of our study was to investigate the ability of endometrial explants an...Background： Estradiol （E2） is required for luteolysis in cows and its injection stimulates prostaglandin F2α （PGF2α） release. The main goal of our study was to investigate the ability of endometrial explants and cells treated with E2 and the calcium ionophore （CI） A23187 to synthesize PGF2α. Results： Treatment with E2 in vivo resulted in a 48.4% increase of PGF2α production by endometrial explants treated in vitro with A23187. Production of PGF20 was better stimulated with A23187 at concentrations of 10^-6 and 10^-5 mol/L compared with other concentrations used. The concentration of PGF2α for untreated bovine endometrial cell cultures was 33.1 pg/mL, while for cultures treated with E2, A23187, or a combination of E2 and A23187, the PGF2α concentration was 32.5, 92.4 and 145.6 pg/mL, respectively. Conclusions： Treatment with A23187 tended to stimulate PGF20 production. In the presence of E2, A23187 significantly stimulated PGF20 synthesis. It appears that A23187 potentiates the effects of E2 with respect to synthesis of endometrial PGF2α in cattle.展开更多
Estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17β-estradiol affected the proliferation of cultured, immature boar Sertoli cells v...Estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17β-estradiol affected the proliferation of cultured, immature boar Sertoli cells via the estrogen receptor β （ERβ） and the cAMP-extracellular signal-regulated kinase （ERK1/2） pathway. Low levels （10-10-10-8 mol L-1） of 17β-estradiol increased cell number, but high levels （10-7-10-6 mol L-1） decreased it （P〈0.05）. Sertoli cell number began to recover for an additional 24 h in the medium without 17β-estradiol （10-6 mol L-l） （P〉0.05）. The effects of 17β-estradiol （10-9 mol L-1） peaked at the first 24 h （P〈0.05）. 17β-estradiol activated ERK1/2 from 5 min to 24 h, but the activiy of ERK1/2 began to decrease after 4 h. Both PD98059 and U0126, two ERK inhibitors, blocked cell division （P〈0.05）. 17β-estradiol （10-10-10-6 mol L-1） dose-dependently increased cAMP production （P 〈 0.05）, and both 17β-estradiol （10-9 mol L-1） and forskolin, which increases cAMP levels, induced cell proliferation and activated ERK1/2 （P〈 0.05）. Rp-cAMP, an antagonist of cAMP, blocked this 17β-estradiol activity （P〈 0.05）. Two estrogen receptor antagonists, ICI 182780 and ERβ antagonist （ERβAnt）, reduced Sertoli cell number, cAMP production and ERK1/2 activation （P〈 0.05）, but ERaAnt did not （P〉 0.05）. Therefore, 17β- estradiol mainly promotes pig Sertoli cell proliferation via ERβ to induce cAMP production and ERK activation to promote cell proliferation.展开更多
BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mR...BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mRNA and Bcl-2 expression, as well as apoptosis and cerebral blood flow, in ovadectomized rats with focal cerebral ischemia following reperfusion. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Central Laboratory, Chongqing Medical University from September to December 2005. MATERIALS： Estradiol benzoate was purchased from Shanghai Ninth Pharmaceutical Factory; corn oil was purchased from Walmart Supercenter; TUNEL kit, rabbit anti-rat Bcl-2 polyclonal antibody, and biotin-labeled goat anti-rabbit antibody were purchased from Wuhan Boster, China. METHODS： Healthy, female, 6-month-old Wistar rats-wild-type and estrogen alpha receptor gene knockout （ERKO）-were randomly divided into estradiol and control groups with 25 animals in each group. The rats were intramuscularly injected with estradiol benzoate （100 μg/kg per day） at 30 days following bilateral ovariectomy or corn oil （1 mL/kg per day） for seven consecutive days. Following administration, cerebral ischemia/reperfusion models were established using the right middle cerebral artery occlusion （MCAO） method. After 30 minutes of MCAO, estradiol and control groups were separately injected with estradiol benzoate and corn oil with the above-mentioned doses. MAIN OUTCOME MEASURES： Cell apoptosis was determined by TUNEL; angiopoietin-1 mRNA and Bcl-2 gene expression was determined, respectively, by immunohistochemical staining and RT-PCR. In addition, changes in cerebral blood flow were measured by laser Doppler flowmetry. RESULTS： Changes in angiopoietin-1 mRNA and cerebral blood flow in estradiol-treated, wild-type, MCAO rats following ischemia/reperfusion were greater than in control rats （P 〈 0.01 or 0.05）. However, no significant difference was observed between estradiol-treated ERKO MCAO rats and control rats. In addition, estradiol-treated wild-type and ERKO MCAO rats exhibited significantly increased Bcl-2 expression （P 〈 0.05） and decreased number of apoptotic cells in brain tissues compared with control groups （P 〈 0.05）. CONCLUSION： Estradiol upregulated angiopoietin-1 mRNA and Bcl-2 expression, suggesting that estradiol might be involved in protective mechanisms of cerebral ischemia/reperfusion injury.展开更多
Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A a...Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.展开更多
The title compound （Z）-ethyl-4-（4-methoxy）benzylidene-2-（3,5-dimethoxyphenyl）- tetrahydrofuran-3,3-dicarboxylate has been synthesized, and its crystal structure was characterized by X-ray single-crystal diffract...The title compound （Z）-ethyl-4-（4-methoxy）benzylidene-2-（3,5-dimethoxyphenyl）- tetrahydrofuran-3,3-dicarboxylate has been synthesized, and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1, with a = 8.140（3）, b = 11.966（4）, c = 13.771（5）Aα= 67.366（4）, β= 85.165（5）, γ= 75.806（4）°, V = 1200.1（7） A3, Z = 2, C26H3008, Mr = 470.50, Dc = 1.302 g/cm^3, F（000） = 500,λ（MoKa） = 0.71073 A, μ= 0.096 mm^-1, R = 0.0659 and wR = 0.1841 for 3080 observed reflections （I 〉 2σ（I））. As a key intermediate of HIV-1 integrase inhibitor, the synthesis and structure confirmation of the title compound are important for further studies.展开更多
Estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （SKP2） plays a central role in mammalian cell cycle progression. The objective of this ...Estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （SKP2） plays a central role in mammalian cell cycle progression. The objective of this study was to determine whether 17β-estradiol can regulate the expression of SKP2, and the Sertoli cell cycle, via estrogen receptor β （ERβ）, the cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA） and extracellular signal-regulated kinase （ERK1/2） pathway. When cultured immature boar Sertoli cells were treated with 17β-estradiol, a time-dependent increase in SKP2 mRNA and protein level was observed by real-time PCR and Western blot, and 17β-estradiol activity peaked at 30 min. Treatment with ICI182780 and ERβ antagonist reduced 17β-estradiol-induced expression of SKP2 and proliferating cell nuclear antigen （PCNA）, while increasing the protein concentration of p27kip1. However, the effect of ERa antagonist on these parameters was lower than that of ICI 182780 and ERβ. Forskolin had a similar effect as 17β-estradiol on the expression of SKP2, PCNA and p27kip1, Rp-cAMP, H-89 and U0126 treatment reduced 17β-estradiol-induced changes, while H-89 also inhibited ERK1/2 activation. Therefore, 17β-estradiol mainly regulates SKP2 mRNA and protein expression via ERβ-cAMP-PKA and ERK1/2 activation. SKP2 and PCNA expression were positively correlated, while increased SKP2 expression likely resulted in p27kip1 degradation.展开更多
The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms i...The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms immune defences.The scope of this review was to elucidate the main human vulnerabilities to Covid-19,including the accumulation of ACE2 receptors in testes,adipose tissue,thyroid,heart and kidneys that escalate viral affinity in males,the aged,and certain medical conditions,including diabetes,CVD,and pulmonary diseases.Pre-existing inflammation inherent in obesity may exacerbate the“cytokine storm,”a rampaging immune reaction during the course of Covid-19 that is deleterious to the host.We examined the molecular dynamics illustrating the action of new therapeutics necessary for Covid-19 patients;the estradiol advantage hypothesis;alternative therapies including hormone replacement procedures and mesenchymal stem cells;plus preventive and protective interventions.The current perspective also explored the primary components of dysregulated health predisposing individuals to Covid-19,including hormonal imbalance,increased lipids and lipoproteins,thyroid dysfunction,degraded fitness,and age-related testosterone decline accompanied by cortisol increase that provokes stress eating behaviours and weight accumulation.Obesity increases the probability of Covid-19 infection due to its abundance of ACE2 receptors;while physical activity may decrease Covid-19 vulnerability,by reducing fat and increasing muscle mass that manifests a relatively inhibited ACE2 expression.Several weight management solutions feature lasers and radiofrequency which diminish subcutaneous adiposity but do not enhance fitness.A data metanalysis of seven recently published clinical studies on 95 obese individuals,73 males and 22 females with an average BMI of 30.9,demonstrated visceral fat reduction combined with increased skeletal muscle mass.It also revealed a statistically significant decrease in BMI,lipids,lipoproteins,inflammation and toxicity as measured by CRP,Creatinine and Bilirubin respectively,juxtaposed by optimally healthier levels of Cortisol,Testosterone,Free T3,IGF-1,Insulin,and the appetite controlling hormones Leptin and Ghrelin.展开更多
基金Supported by the Hebei Province Medical Science Research Key Project(No.20210276).
文摘Objective The aim of the study was to determine the association of urinary levels of estradiol(E_(2))and 2-methoxyestradiol(2-MeOE_(2))with the occurrence and development of endometrial cancer.Methods In this case-control study,24-h urine specimens were collected from 28 postmenopausal patients with endometrial cancer and 28 postmenopausal healthy female controls.The concentration of 2-MeOE_(2) was determined using liquid chromatography-mass spectrometry with hollow fiber liquid-phase microextraction.The concentration of E_(2) was determined using an enzyme-linked immunosorbent assay.Results Estrogen levels were different between the patients with endometrial cancer and controls.The relative quantity of E_(2) in the case group was higher than that in the control group(P<0.05),whereas that of 2-MeOE_(2) was lower in the case group than that in the control group(P<0.05).The ratio of E_(2)-to-2-MeOE_(2) in the case group was significantly higher than that in the control group(P<0.05).Conclusion The results of this study indicate an imbalance of estrogen metabolites in endometrial carcinogenesis.Reduced 2-MeOE_(2) levels and elevated E_(2)-to-2-MeOE_(2) ratio may be used as potential biomarkers for the risk assessment of estrogen-induced endometrial cancer.
基金funded by Fundao de Amparo à Pesquisa do Estado de So Paulo (FAPESP)
文摘Background： Estradiol （E2） is required for luteolysis in cows and its injection stimulates prostaglandin F2α （PGF2α） release. The main goal of our study was to investigate the ability of endometrial explants and cells treated with E2 and the calcium ionophore （CI） A23187 to synthesize PGF2α. Results： Treatment with E2 in vivo resulted in a 48.4% increase of PGF2α production by endometrial explants treated in vitro with A23187. Production of PGF20 was better stimulated with A23187 at concentrations of 10^-6 and 10^-5 mol/L compared with other concentrations used. The concentration of PGF2α for untreated bovine endometrial cell cultures was 33.1 pg/mL, while for cultures treated with E2, A23187, or a combination of E2 and A23187, the PGF2α concentration was 32.5, 92.4 and 145.6 pg/mL, respectively. Conclusions： Treatment with A23187 tended to stimulate PGF20 production. In the presence of E2, A23187 significantly stimulated PGF20 synthesis. It appears that A23187 potentiates the effects of E2 with respect to synthesis of endometrial PGF2α in cattle.
基金supported by the National Natural Science Foundation of China(30270955)the Foundamental Research Funds for the Central Universities,China(XDJK2009B035)
文摘Estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17β-estradiol affected the proliferation of cultured, immature boar Sertoli cells via the estrogen receptor β （ERβ） and the cAMP-extracellular signal-regulated kinase （ERK1/2） pathway. Low levels （10-10-10-8 mol L-1） of 17β-estradiol increased cell number, but high levels （10-7-10-6 mol L-1） decreased it （P〈0.05）. Sertoli cell number began to recover for an additional 24 h in the medium without 17β-estradiol （10-6 mol L-l） （P〉0.05）. The effects of 17β-estradiol （10-9 mol L-1） peaked at the first 24 h （P〈0.05）. 17β-estradiol activated ERK1/2 from 5 min to 24 h, but the activiy of ERK1/2 began to decrease after 4 h. Both PD98059 and U0126, two ERK inhibitors, blocked cell division （P〈0.05）. 17β-estradiol （10-10-10-6 mol L-1） dose-dependently increased cAMP production （P 〈 0.05）, and both 17β-estradiol （10-9 mol L-1） and forskolin, which increases cAMP levels, induced cell proliferation and activated ERK1/2 （P〈 0.05）. Rp-cAMP, an antagonist of cAMP, blocked this 17β-estradiol activity （P〈 0.05）. Two estrogen receptor antagonists, ICI 182780 and ERβ antagonist （ERβAnt）, reduced Sertoli cell number, cAMP production and ERK1/2 activation （P〈 0.05）, but ERaAnt did not （P〉 0.05）. Therefore, 17β- estradiol mainly promotes pig Sertoli cell proliferation via ERβ to induce cAMP production and ERK activation to promote cell proliferation.
基金Supported by:the Natural Science Foundation of Chongqing,No. CSTC2006EB5030
文摘BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mRNA and Bcl-2 expression, as well as apoptosis and cerebral blood flow, in ovadectomized rats with focal cerebral ischemia following reperfusion. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Central Laboratory, Chongqing Medical University from September to December 2005. MATERIALS： Estradiol benzoate was purchased from Shanghai Ninth Pharmaceutical Factory; corn oil was purchased from Walmart Supercenter; TUNEL kit, rabbit anti-rat Bcl-2 polyclonal antibody, and biotin-labeled goat anti-rabbit antibody were purchased from Wuhan Boster, China. METHODS： Healthy, female, 6-month-old Wistar rats-wild-type and estrogen alpha receptor gene knockout （ERKO）-were randomly divided into estradiol and control groups with 25 animals in each group. The rats were intramuscularly injected with estradiol benzoate （100 μg/kg per day） at 30 days following bilateral ovariectomy or corn oil （1 mL/kg per day） for seven consecutive days. Following administration, cerebral ischemia/reperfusion models were established using the right middle cerebral artery occlusion （MCAO） method. After 30 minutes of MCAO, estradiol and control groups were separately injected with estradiol benzoate and corn oil with the above-mentioned doses. MAIN OUTCOME MEASURES： Cell apoptosis was determined by TUNEL; angiopoietin-1 mRNA and Bcl-2 gene expression was determined, respectively, by immunohistochemical staining and RT-PCR. In addition, changes in cerebral blood flow were measured by laser Doppler flowmetry. RESULTS： Changes in angiopoietin-1 mRNA and cerebral blood flow in estradiol-treated, wild-type, MCAO rats following ischemia/reperfusion were greater than in control rats （P 〈 0.01 or 0.05）. However, no significant difference was observed between estradiol-treated ERKO MCAO rats and control rats. In addition, estradiol-treated wild-type and ERKO MCAO rats exhibited significantly increased Bcl-2 expression （P 〈 0.05） and decreased number of apoptotic cells in brain tissues compared with control groups （P 〈 0.05）. CONCLUSION： Estradiol upregulated angiopoietin-1 mRNA and Bcl-2 expression, suggesting that estradiol might be involved in protective mechanisms of cerebral ischemia/reperfusion injury.
文摘Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.
基金supported by the National Natural Science Foundation of China (No. 30572238)
文摘The title compound （Z）-ethyl-4-（4-methoxy）benzylidene-2-（3,5-dimethoxyphenyl）- tetrahydrofuran-3,3-dicarboxylate has been synthesized, and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1, with a = 8.140（3）, b = 11.966（4）, c = 13.771（5）Aα= 67.366（4）, β= 85.165（5）, γ= 75.806（4）°, V = 1200.1（7） A3, Z = 2, C26H3008, Mr = 470.50, Dc = 1.302 g/cm^3, F（000） = 500,λ（MoKa） = 0.71073 A, μ= 0.096 mm^-1, R = 0.0659 and wR = 0.1841 for 3080 observed reflections （I 〉 2σ（I））. As a key intermediate of HIV-1 integrase inhibitor, the synthesis and structure confirmation of the title compound are important for further studies.
基金grants from the National Natural Science Foundation of China(31072183)the Fundamental Research Funds for the Central Universities,China(XDJK2009B035)
文摘Estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （SKP2） plays a central role in mammalian cell cycle progression. The objective of this study was to determine whether 17β-estradiol can regulate the expression of SKP2, and the Sertoli cell cycle, via estrogen receptor β （ERβ）, the cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA） and extracellular signal-regulated kinase （ERK1/2） pathway. When cultured immature boar Sertoli cells were treated with 17β-estradiol, a time-dependent increase in SKP2 mRNA and protein level was observed by real-time PCR and Western blot, and 17β-estradiol activity peaked at 30 min. Treatment with ICI182780 and ERβ antagonist reduced 17β-estradiol-induced expression of SKP2 and proliferating cell nuclear antigen （PCNA）, while increasing the protein concentration of p27kip1. However, the effect of ERa antagonist on these parameters was lower than that of ICI 182780 and ERβ. Forskolin had a similar effect as 17β-estradiol on the expression of SKP2, PCNA and p27kip1, Rp-cAMP, H-89 and U0126 treatment reduced 17β-estradiol-induced changes, while H-89 also inhibited ERK1/2 activation. Therefore, 17β-estradiol mainly regulates SKP2 mRNA and protein expression via ERβ-cAMP-PKA and ERK1/2 activation. SKP2 and PCNA expression were positively correlated, while increased SKP2 expression likely resulted in p27kip1 degradation.
文摘The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors,or the infectious RNA replication that often overwhelms immune defences.The scope of this review was to elucidate the main human vulnerabilities to Covid-19,including the accumulation of ACE2 receptors in testes,adipose tissue,thyroid,heart and kidneys that escalate viral affinity in males,the aged,and certain medical conditions,including diabetes,CVD,and pulmonary diseases.Pre-existing inflammation inherent in obesity may exacerbate the“cytokine storm,”a rampaging immune reaction during the course of Covid-19 that is deleterious to the host.We examined the molecular dynamics illustrating the action of new therapeutics necessary for Covid-19 patients;the estradiol advantage hypothesis;alternative therapies including hormone replacement procedures and mesenchymal stem cells;plus preventive and protective interventions.The current perspective also explored the primary components of dysregulated health predisposing individuals to Covid-19,including hormonal imbalance,increased lipids and lipoproteins,thyroid dysfunction,degraded fitness,and age-related testosterone decline accompanied by cortisol increase that provokes stress eating behaviours and weight accumulation.Obesity increases the probability of Covid-19 infection due to its abundance of ACE2 receptors;while physical activity may decrease Covid-19 vulnerability,by reducing fat and increasing muscle mass that manifests a relatively inhibited ACE2 expression.Several weight management solutions feature lasers and radiofrequency which diminish subcutaneous adiposity but do not enhance fitness.A data metanalysis of seven recently published clinical studies on 95 obese individuals,73 males and 22 females with an average BMI of 30.9,demonstrated visceral fat reduction combined with increased skeletal muscle mass.It also revealed a statistically significant decrease in BMI,lipids,lipoproteins,inflammation and toxicity as measured by CRP,Creatinine and Bilirubin respectively,juxtaposed by optimally healthier levels of Cortisol,Testosterone,Free T3,IGF-1,Insulin,and the appetite controlling hormones Leptin and Ghrelin.
