Leuprolide

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GnRH secreted from the hypothalamus in a continuous fashion is actually inhibitory to FSH/LH secretion. Pulsatile secretion of GnRH allows for FSH/LH secretion. Therefore, dosing leuprolide (GnRH analog) in a similar pulsatile fashion will allow for FSH/LH secretion and thus ovulation if that patient is deficient in any of these hormones.
 
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dyspareunia said:
Can someone explain how pulsatile dosing can treat infertility?
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Leuprolide - in lieu of GnRH
Pulses of GnRH will stimulate the release of FSH and LH. LH will act on Thecal cells to make androstenedione (AD) and then under the influence of FSH, Granulosa will convert the AD to Estradiole via Aromatase. Estradiole (which is the most potent form of estrongen) can positively regulate GnRH that leads to an LH surge and consequently an ovulation.
 
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Its well know that Leuprolide can act both ways and there are many questions i saw regarding it in UW, Kap Qbank, Rx, etc..
I HAD A DEEPER QUESTION...
Does anyone know the exact mechanism why this happens ?
I didnt read it anywhere but there must be a cellular - level reasoning behind why the same hormone is stimulatory and inhibitory ?
IDK why but whenever i think of it...i remember how insulin (and all hormones in general) continuously stimulating a cell lead to down regulation of the receptor on the cell.. (like insulin and obesity causing DM II)
Is this the real reason? ...just my hypothesis
Please help if u know why.. 🙂
 
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DrTejIndia said:
Its well know that Leuprolide can act both ways and there are many questions i saw regarding it in UW, Kap Qbank, Rx, etc..
I HAD A DEEPER QUESTION...
Does anyone know the exact mechanism why this happens ?
I didnt read it anywhere but there must be a cellular - level reasoning behind why the same hormone is stimulatory and inhibitory ?
IDK why but whenever i think of it...i remember how insulin (and all hormones in general) continuously stimulating a cell lead to down regulation of the receptor on the cell.. (like insulin and obesity causing DM II)
Is this the real reason? ...just my hypothesis
Please help if u know why.. 🙂
Click to expand...

I think that with the constant GnRH supply, there is desensitization occurring. You can vary LH and FSH release from how frequently you give GnRH - at a greater frequent, you will have more LH and at a lower frequently, you will get more FSH - it also has to do with glycosylation of LH and FSH (I do not know the exact mechanism - but glycosylation is related to pulsatile GnRH and less glycosylated FSH/LH means more potent but shorter half life). I don't think we need to know for the Steps. I just know them from my class.
 
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I think the relevant basic science is that LH/FSH are regulated in pulsatile fashion so it only makes sense to administer GnRH agonists in a pulsatile fashion.
 
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DrTejIndia said:
Its well know that Leuprolide can act both ways and there are many questions i saw regarding it in UW, Kap Qbank, Rx, etc..
I HAD A DEEPER QUESTION...
Does anyone know the exact mechanism why this happens ?
I didnt read it anywhere but there must be a cellular - level reasoning behind why the same hormone is stimulatory and inhibitory ?
IDK why but whenever i think of it...i remember how insulin (and all hormones in general) continuously stimulating a cell lead to down regulation of the receptor on the cell.. (like insulin and obesity causing DM II)
Is this the real reason? ...just my hypothesis
Please help if u know why.. 🙂
Click to expand...
you mean via tachyphylaxis?
 
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