Genes and Stress can cause PCO; How metformin will make a solution?? How does polymorphisms in both subunits of the IL-6 receptor affects the woman?? How does Argo polymorphism in the gp130 gene is more frequent in control health women as c compared with hyperandrogenic patients: . Such control women had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations and a significant decrease in free testosterone levels, suggesting that this polymorphism might have a protective effect against androgen excess.
Arg148 allele of the Glee 148 Argo polymorphism in the gp130 gene ILr6::- This cytokine seems to be implicated in insulin resistance mechanism, and increased levels were found in peritoneal fluid of anovulatory PCOS patients, suggesting a role in the pathogenesis of hyperandrogenic disorders . Common polymorphisms in both subunits of the IL-6 receptor have been studied, and the Arg148 allele of the Glee 148
What explanation we have to account for more AFC in PCO women? Any Genetic explanation?? Ans: Let us quickly recapitulate the physiology of folliculogenesis in healthy women?? In a normal cycle, only the dominant follicle responds to LH action when it reaches 10 mm in diameter. In PCOS patients, the response to LH occurs inappropriately in smaller follicles; a large number of antral follicles reach a terminal differentiation before the appropriate time, producing a larger amount of steroids and inhibin B that have a negative feedback on the production of FSH: the result is the arrest of follicular growth.
In PCOS patients, the response to LH occurs inappropriately in smaller follicles; a large number of antral follicles reach a terminal differentiation before the appropriate time, producing a larger amount of steroids and inhibin B that have a negative feedback on the production of FSH: the result is the arrest of follicular growth.
It has been shown that polycystic ovary presents a greater number of small antral follicles (2-9 mm in diameter) than the normal ovary. This morphological scenario could be the consequence of a potential dysregulation of the recruitment mechanism of primordial follicles that, on the contrary, are present in physiological number. But we have to remember that the final pathway of follicular growth, which is gonadotropin dependent, is blocked in the majority of PCOS patients, and it is the basis of anovu-lation and oligo-/amenorrhea.
Can the clinical, features of P CO be so silent that we even the senior physicians may miss the very early symptoms of PCO? As discussed in details about 5 genes that are involved in PCO, it may be possible that many more genes may be responsible for PCO . Such mutation are just possible. Admittedly, the etiology of this syndrome is still partly unknown, but it is likely to be multifactorial. The most significant theories are explained below:
* Exaggerated Adrenarche: the primary stimulus. & , which provides, in response to a stress condition, a transient adrenal androgen hypersecretion, triggering an abnormal pattern of the pituitary gonadotropins’ pulsatility. It is possible that PCOS might be established and maintained in response to an abnormal adrenal hypersecretion of androgens due to congenital adrenal enzyme deficiency. Researchers have suggested that an important etiopathogenetic model involving stress as the primary stimulus. & , which provides, in response to a stress condition, a transient adrenal androgen hypersecretion, triggering an abnormal pattern of the pituitary gonadotropins’ pulsatility. As puberty progresses, the adrenal cortex is replaced by ovaries in maintaining the hypersecretion of androgens.
Finally, the increase in ovarian androgen level changes adrenal specific enzyme activities involved in the process of steroidogenesis .
• Abnormal Secretion of Gonadotropins: The sequence of events are like this. Initially there is stress induced elevated endogenous Opioid tone- might cause an exceeding GnRH release - followed by abnormal LH pulsatility The high levels of LH in women with PCOS are due to greater amplitude of the peaks of this hormone and its increased frequency of pulsatility; on the contrary, the average concentration of FSH is mostly decreased. The high levels of LH are not caused by an inability of the hypothalamic-pituitary axis to respond to the negative feedback exerted by estrogen, but it might be caused by the high pituitary sensitivity to LH-RH. The chronically elevated and acyclic levels of estrogens in PCOS patients may, in turn, increase both the basal levels of LH and LH response to GnRH.
Moreover, an elevated endogenous Opioid tone might cause an exceeding GnRH release with a following abnormal LH pulsatility, causing increased level of LH- dependent ovarian androgens .
Arg148 allele of the Glee 148 Argo polymorphism in the gp130 gene ILr6::- This cytokine seems to be implicated in insulin resistance mechanism, and increased levels were found in peritoneal fluid of anovulatory PCOS patients, suggesting a role in the pathogenesis of hyperandrogenic disorders . Common polymorphisms in both subunits of the IL-6 receptor have been studied, and the Arg148 allele of the Glee 148
What explanation we have to account for more AFC in PCO women? Any Genetic explanation?? Ans: Let us quickly recapitulate the physiology of folliculogenesis in healthy women?? In a normal cycle, only the dominant follicle responds to LH action when it reaches 10 mm in diameter. In PCOS patients, the response to LH occurs inappropriately in smaller follicles; a large number of antral follicles reach a terminal differentiation before the appropriate time, producing a larger amount of steroids and inhibin B that have a negative feedback on the production of FSH: the result is the arrest of follicular growth.
In PCOS patients, the response to LH occurs inappropriately in smaller follicles; a large number of antral follicles reach a terminal differentiation before the appropriate time, producing a larger amount of steroids and inhibin B that have a negative feedback on the production of FSH: the result is the arrest of follicular growth.
It has been shown that polycystic ovary presents a greater number of small antral follicles (2-9 mm in diameter) than the normal ovary. This morphological scenario could be the consequence of a potential dysregulation of the recruitment mechanism of primordial follicles that, on the contrary, are present in physiological number. But we have to remember that the final pathway of follicular growth, which is gonadotropin dependent, is blocked in the majority of PCOS patients, and it is the basis of anovu-lation and oligo-/amenorrhea.
Can the clinical, features of P CO be so silent that we even the senior physicians may miss the very early symptoms of PCO? As discussed in details about 5 genes that are involved in PCO, it may be possible that many more genes may be responsible for PCO . Such mutation are just possible. Admittedly, the etiology of this syndrome is still partly unknown, but it is likely to be multifactorial. The most significant theories are explained below:
* Exaggerated Adrenarche: the primary stimulus. & , which provides, in response to a stress condition, a transient adrenal androgen hypersecretion, triggering an abnormal pattern of the pituitary gonadotropins’ pulsatility. It is possible that PCOS might be established and maintained in response to an abnormal adrenal hypersecretion of androgens due to congenital adrenal enzyme deficiency. Researchers have suggested that an important etiopathogenetic model involving stress as the primary stimulus. & , which provides, in response to a stress condition, a transient adrenal androgen hypersecretion, triggering an abnormal pattern of the pituitary gonadotropins’ pulsatility. As puberty progresses, the adrenal cortex is replaced by ovaries in maintaining the hypersecretion of androgens.
Finally, the increase in ovarian androgen level changes adrenal specific enzyme activities involved in the process of steroidogenesis .
• Abnormal Secretion of Gonadotropins: The sequence of events are like this. Initially there is stress induced elevated endogenous Opioid tone- might cause an exceeding GnRH release - followed by abnormal LH pulsatility The high levels of LH in women with PCOS are due to greater amplitude of the peaks of this hormone and its increased frequency of pulsatility; on the contrary, the average concentration of FSH is mostly decreased. The high levels of LH are not caused by an inability of the hypothalamic-pituitary axis to respond to the negative feedback exerted by estrogen, but it might be caused by the high pituitary sensitivity to LH-RH. The chronically elevated and acyclic levels of estrogens in PCOS patients may, in turn, increase both the basal levels of LH and LH response to GnRH.
Moreover, an elevated endogenous Opioid tone might cause an exceeding GnRH release with a following abnormal LH pulsatility, causing increased level of LH- dependent ovarian androgens .
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