| 1. |
|
|
| 2. |
- Feng, Yi, et al.
(author)
-
Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electro-acupuncture.
- 2009
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:8
-
Journal article (peer-reviewed)abstract
- Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5alpha-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4-5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS.
|
|
| 3. |
- Friberg, P. Anders, 1976, et al.
(author)
-
Apoptotic effects of a progesterone receptor antagonist on rat granulosa cells are not mediated via reduced protein isoprenylation.
- 2007
-
In: Molecular reproduction and development. - : Wiley. - 1040-452X .- 1098-2795. ; 74:10, s. 1317-26
-
Journal article (peer-reviewed)abstract
- Progesterone is a survival factor in rat periovulatory granulosa cells. The mechanisms involved are unclear but progesterone receptor (PGR) antagonists have been shown to inhibit cholesterol synthesis and induce apoptosis. Furthermore, reports suggest that statins induce apoptosis by inhibition of protein isoprenylation. Statins inhibit the rate-limiting step of the cholesterol synthesis, thereby reducing availability of intermediates used for the post-translational isoprenylation process. It has been suggested that PGR antagonists in a similar manner induce apoptosis by decreasing cholesterol synthesis and thereby protein isoprenylation. In this study we hypothesized that the mechanism by which the nuclear PGR antagonist Org 31,710 induces apoptosis in rat periovulatory granulosa cells, is by decreasing cholesterol synthesis and thereby general cell protein isoprenylation. Incubation of isolated granulosa cells with Org 31,710 or simvastatin for 22 hr resulted in increased apoptosis and reduced cholesterol synthesis. However, simvastatin caused a substantial inhibition of cholesterol synthesis after 6 hr in culture without inducing apoptosis. In contrast, Org 31,710 had only a modest effect on cholesterol synthesis after 6 hr while it significantly induced apoptosis. Addition of isoprenylation substrates partially reversed apoptosis induced by simvastatin and to a lesser extent apoptosis induced by Org 31,710. In addition, and in contrast to Org 31,710, simvastatin caused a decrease in isoprenylation of a selected isoprenylation marker protein, the Ras-related protein RAB11. In conclusion, we demonstrate that the PGR antagonist inhibits cholesterol synthesis in granulosa cells but reduced protein isoprenylation is not the mediating mechanism of increased apoptosis as previously hypothesized.
|
|
| 4. |
- Friberg, P. Anders, 1976, et al.
(author)
-
Dominant role of nuclear progesterone receptor in the control of rat periovulatory granulosa cell apoptosis.
- 2009
-
In: Biology of reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 80:6, s. 1160-7
-
Journal article (peer-reviewed)abstract
- In this study, it was hypothesized that progesterone (P4) acts as a survival factor primarily by actions of the classic nuclear progesterone receptor (PGR) signaling pathway in rat periovulatory granulosa cells. Granulosa cells were isolated from immature female rats primed with equine chorionic gonadotropin/human chorionic gonadotropin and treated in vitro with PGR antagonists. As little as 10 nM of two different PGR antagonists (Org 31710 and RU 486) increased apoptosis measured as caspase 3/7 activity, which was reversed by cotreatment with the progestin R5020. Concurrently, P4 synthesis was decreased. Inhibition of P4 synthesis by cyanoketone similarly induced apoptosis but required greater inhibition of P4 synthesis than that seen after treatment with PGR antagonists. Therefore, the induction of apoptosis by PGR antagonists cannot be explained by decreased P4 synthesis alone. Low concentrations of R5020 also completely reversed the effects of cyanoketone. Inhibition of P4 synthesis was more effective in inducing apoptosis than treatment with PGR antagonists. However, cotreatment with PGR antagonists protected cells from the additional effects of cyanoketone, indicating partial agonist effects of the antagonists and a dominating role for PGR in P4-mediated regulation of apoptosis. Progesterone receptor membrane component 1 (PGRMC1) was expressed in granulosa cells; however, an anti-PGRMC1 antibody did not induce apoptosis in periovulatory granulosa cells. Neither anti-PGRMC1 nor P4 or cyanoketone affected apoptosis of immature granulosa cells. In conclusion, we show that P4 regulates apoptosis in periovulatory granulosa cells by acting via the classic nuclear receptor.
|
|
| 5. |
|
|
| 6. |
- Nilsson, Louise, 1975, et al.
(author)
-
Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue
- 2005
-
In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 331
-
Journal article (peer-reviewed)abstract
- Adiponectin is a hormone secreted from adipose tissue, and serum levels are decreased with obesity and insulin resistance. Because prolactin (PRL) and growth hormone (GH) can affect insulin sensitivity, we investigated the effects of these hormones on the regulation of adiponectin in human adipose tissue in vitro and in rodents in vivo. Adiponectin secretion was significantly suppressed by PRL and GH in in vitro cultured human adipose tissue. Furthermore, PRL increased adiponectin receptor 1 (AdipoR1) mRNA expression and GH decreased AdipoR2 expression in the cultured human adipose tissue. In transgenic mice expressing GH, and female mice expressing PRL, serum levels of adiponectin were decreased. In contrast, GH receptor deficient mice had elevated adiponectin levels, while PRL receptor deficient mice were unaffected. In conclusion, we demonstrate gene expression of AdipoR1 and AdipoR2 in human adipose tissue for the first time, and show that these are differentially regulated by PRL and GH. Both PRL and GH reduced adiponectin secretion in human adipose tissue in vitro and in mice in vivo. Decreased serum adiponectin levels have been associated with insulin resistance, and our data in human tissue and in transgenic mice suggest a role for adiponectin in PRL and GH induced insulin resistance.
|
|
| 7. |
- Nilsson, Louise, 1975, et al.
(author)
-
Prolactin suppresses malonyl-CoA concentration in human adipose tissue.
- 2009
-
In: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 41:10, s. 747-51
-
Journal article (peer-reviewed)abstract
- Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed lipogenesis could contribute to an insulin resistant state with consequences for the health.
|
|
| 8. |
- Nutu, Magdalena, 1967, et al.
(author)
-
Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in ciliated epithelial cells of mouse and human fallopian tubes.
- 2009
-
In: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 7:89
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The controlled beating of cilia of the fallopian tube plays an important role in facilitating the meeting of gametes and subsequently transporting the fertilized egg to its implantation site. Rapid effects of progesterone on ciliary beat frequency have been reported in the fallopian tubes of cows, but the identity of the receptors mediating this non-genomic action of progesterone is not known. We recently identified a member of the non-genomic membrane progesterone receptor family, mPR gamma, as a candidate for mediating these actions of progesterone. Here, we investigated the possible presence of a related receptor, mPR beta, in the fallopian tubes of mice and women as well as the possible hormonal regulation of mPR beta and gamma. METHODS: Western blot and immunohistochemistry with specific antibodies were used to characterize the expression and cellular localization of the mPRs in mouse and human tissues. Taqman (Quantitative Polymerase Chain Reaction) assays were used to quantify mRNA levels in the fallopian tubes of two different mouse models after injections with different hormones and specific antagonists. RESULTS: In the fallopian tubes of both mouse and human, the expression of mPR beta and mPR gamma proteins was exclusively found in the ciliated cells. Whereas mPR beta was found on the cilia, mPR gamma was localized at the base of the same ciliated cells, as previously reported. In gonadotropin-primed mice, both mPRs genes were down-regulated after an injection with progesterone. Treatment with estradiol rapidly down-regulated the level of mPR beta mRNA and protein in immature mice. The mPR gamma protein was down-regulated around the time of ovulation in cycling women, similar to the regulation observed in mice stimulated to ovulate via gonadotropin injections. CONCLUSION: Our findings show the presence and hormonal regulation of two distinct mPRs associated with the cilia of the fallopian tubes in both mice and women. It is hypothesized that these receptors are involved in the control of ciliary movement and, thus, gamete transport in the fallopian tubes of mammals.
|
|
| 9. |
- Nutu, Magdalena, 1967, et al.
(author)
-
Membrane progesterone receptor gamma: tissue distribution and expression in ciliated cells in the fallopian tube.
- 2007
-
In: Molecular reproduction and development. - : Wiley. - 1040-452X .- 1098-2795. ; 74:7, s. 843-50
-
Journal article (peer-reviewed)abstract
- Non-genomic, rapid actions of steroids have long been known, suggesting the possible presence of non-classical steroid receptors. A membrane receptor for progestins (mPR) was recently described in the spotted seatrout, and transcripts of three related receptors (alpha, beta, and gamma) were subsequently identified in other species including human and mouse. To begin exploring the roles of mPRgamma in mammals, we have generated an antibody against this receptor. The specificity of the antibody was demonstrated by both overexpression and RNA interference experiments. Using the antibody, we show that mPRgamma is expressed in female mouse reproductive tissues such as ovary and fallopian tube, and also in the lung and liver of both sexes. Immunohistochemical studies revealed that mPRgamma is associated with the apical membrane of ciliated cells facing the lumen of the fallopian tube. The presence of mPRgamma in ciliated cells of the fallopian tube was also demonstrated in human samples. Rapid effects of progesterone on ciliary beat frequency in the fallopian tube have recently been reported. Together, this suggests a common role for mPRgamma in the regulation of ciliary activity in the fallopian tube and thus gamete transport in mammals. The presence of mPRgamma in lung and liver of mice suggests that the receptor mediates the actions of progesterone outside the reproductive tract as well.
|
|
| 10. |
|
|
