Effect of the antioxidant TK 12627 (Irganox) on monodeiodination and on the levels of messenger ribonucleic acid of 5′-deiodinase type I and spot 14

1993 ◽  
Vol 128 (5) ◽  
pp. 451-458 ◽  
Author(s):  
H Liang ◽  
O Morin ◽  
AG Burger
Keyword(s):  
Thyroid Hormone ◽  
Ribonucleic Acid ◽  
Target Genes ◽  
Liver Microsomes ◽  
Triethylene Glycol ◽  
Type I ◽  
Mrna Levels ◽  
Messenger Ribonucleic Acid ◽  
Spot 14

Until now, most potent inhibitors of monodeiodination are iodinated, propylthiouracil being an exception. We report here studies on a new non-iodinated substance, triethylene glycol bis-3-(3-tertbutyl-4-hydroxy-5-methyl-phenyl) propionate (TK 12627 or Irganox), which is used as a very efficient antioxidant in the chemistry of plastics. The studies were performed with 23 hypothyroid rats that received Irganox in their daily food (8 mg·day−1·(100 g body wt)−1) for 3 weeks. Thyroxine (T4) metabolism was studied by implanting minipumps delivering 2.3 nmol T4·dayℒ1·(100 g body wt)ℒ1 for 1 week. On day 1 before sacrifice, another minipump containing [125I]-3,5,3′-triiodothyronine (T3, 2.6 μCi/day) and [131I]-3,3′,5′-triiodothyronine (rT3, 2.1 μCi/day) was implanted. The results showed that with Irganox treatment serum T4 concentrations were higher (p<0.05). Serum T3 concentrations markedly decreased (1.07±0.07 vs 0.65±0.04 nmol/l), accompanied by a decrease of free T3 concentrations (p<0.001). Serum rT3 concentrations increased by 50% (p<0.001). Serum thyrotropin levels were mostly unmeasurable. The plasma clearance rate decreased slightly for T4 (19%, p<0.05) and remarkably for rT3 (46.7%, p<0.001). The conversion rate of T4 to rT3 did not change. Deiodinase type I (5′D-I) activity decreased in both liver and kidney tissues by 54% and 52%, respectively, and correlated with T3 (r2 = 0.79 and 0.65, respectively). Brain deiodinase type III (5D-III) was unchanged and type II (5′D-II) was unmeasurable. The relative abundance of 5′D-I messenger ribonucleic acid (mRNA) levels decreased by 40% in liver and 42% in kidney and it correlated with serum T3 levels also (r2 = 0.71 and 0.72, respectively). The amount of hepatic spot 14 mRNA also decreased by 41% (p<0.05); however, the abundance of hepatic beta-actin mRNA was not affected by the treatment. In an additional experiment. Irganox-treated rats received 2 nmol T3 ·day−1·(100 g body wt)−1; this treatment prevented the changes in mRNA levels of 5′D-I and spot 14 but did not prevent the decrease of 5′D-I activity in either liver or kidney. In vitro studies with liver microsomes showed that Irganox is a specific non-competitive inhibitor of 5′D-I activity, with a Ki of 12 μmol/l. These studies suggest that Irganox, by inhibiting 5′D-I activity, can effect thyroid hormone monodeiodination followed by changes of mRNA levels of some thyroid hormone-dependent target genes.

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

2020 ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie Hicks ◽  
Julie A Long ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Differential Responsiveness ◽  
Hpt Axis

Abstract Background: High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells.Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Furthermore, thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone being more detrimental in HEPH and estradiol stimulatory effects being more prominent in LEPH. Differential responsiveness to thyroid hormone and estradiol pretreatment may be due to desensitization of target genes to thyroid hormone and estradiol in LEPH and HEPH, respectively, in response general up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the full role that the HPT axis and beta-estradiol upstream regulation play in egg production rates in turkey hens.

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

2020 ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie Hicks ◽  
Julie A Long ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Upstream Regulator ◽  
Hpt Axis

Abstract Background: High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells.Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I

1995 ◽  
Vol 132 (6) ◽  
pp. 751-758 ◽  
Author(s):  
Cristiana E Juge-Aubry ◽  
Odette Morin ◽  
Agnés T Pernin ◽  
Hong Liang ◽  
Jacques Philippe ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Gradual Increase ◽  
Biological Effects ◽  
Type I ◽  
Mrna Levels ◽  
Spot 14 ◽  
Stopping Treatment ◽  
Serum Tsh ◽  
Tsh Levels

Juge-Aubry CE, Morin 0, Pernin AT, Liang H, Phillipe J, Burger AG. Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I. Eur J Endocrinol 1995;132:751–8. The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T4) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T4 and Triac, hypothyroid rats (N= 84) received over 6 days' injections of lOnmol Triac or 2 nmol T4/100 g body wt per day. Biological effects of Triac and T4 were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 ± 1.8 μ/l (hypothyroid 14.5 ± 0.8 μg/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T4 injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in β-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5′-deiodinase type I (5′D-I), The 6-day treatment with Triac had a markedly stronger effect on 5′D-I enzyme activity and mRNA levels than treatment with T4. Again, the effect disappeared slowly because hepatic activity was still above control levels 8 days after treatment. The mRNA levels of spot 14 also were higher with Triac. However, 4 days after stopping treatment with both hormones, mRNA levels had returned to hypothyroid values. These data suggest that at the pituitary level one can distinguish between rapid and slower effects. For 5′D-I activity, however, the effects are longlasting and there is no apparent difference in the duration of the effects between Triac or T4. They last much longer than the injected hormone. Our results show that even for parameters closely controlled by thyroid hormones, the expression and duration of thyroid hormone effects vary markedly, not only from organ to organ TSH/5′D-I but also within the same organ, depending on the parameters (5′D-I/ spot 14). Cristiana E Juge-Aubry, Thyroid Unit, Hôpital Cantonal Universitaire, 1211 Geneva 14, Switzerland

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

2020 ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie Hicks ◽  
Julie A Long ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Upstream Regulator ◽  
Hpt Axis

Abstract Background: High egg producing hens ( HEPH ) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal ( HPG ) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone ( GnRH ) stimulation in the pituitary when compared to low egg producing hens ( LEPH ). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes ( DEGs ) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid ( HPT ) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie A. Hicks ◽  
Julie A. Long ◽  
Tom E. Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Upstream Regulator ◽  
Hpt Axis

Abstract Background High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

2020 ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie Hicks ◽  
Julie A Long ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Upstream Regulator ◽  
Hpt Axis

Abstract Background: High egg producing hens ( HEPH ) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal ( HPG ) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone ( GnRH ) stimulation in the pituitary when compared to low egg producing hens ( LEPH ). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes ( DEGs ) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid ( HPT ) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

scholarly journals Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

2020 ◽  
Author(s):  
Kristen Brady ◽  
Hsiao-Ching Liu ◽  
Julie Hicks ◽  
Julie A Long ◽  
Tom E Porter
Keyword(s):  
Thyroid Hormone ◽  
Transcriptome Analysis ◽  
Egg Production ◽  
Target Genes ◽  
Mrna Levels ◽  
Hpg Axis ◽  
Subunit Mrna ◽  
Upstream Regulator ◽  
Hpt Axis

Abstract Background: High egg producing hens ( HEPH ) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal ( HPG ) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone ( GnRH ) stimulation in the pituitary when compared to low egg producing hens ( LEPH ). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes ( DEGs ) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid ( HPT ) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

scholarly journals Differential Effects of Gonadotropin-Releasing Hormone (GnRH) Pulse Frequency on Gonadotropin Subunit and GnRH Receptor Messenger Ribonucleic Acid Levels in Vitro*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1224-1231 ◽  
Author(s):  
Ursula B. Kaiser ◽  
Andrzej Jakubowiak ◽  
Anna Steinberger ◽  
William W. Chin
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Pulse Frequency ◽  
Gnrh Receptor ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Subunit Gene ◽  
Differential Effects ◽  
Messenger Ribonucleic Acid

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

Sign in / Sign up

Export Citation Format

Share Document