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[BoneNibbler]

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question about pituitary adenoma?

TX- bromocriptine (DA agonist)---> shrinks tumor

How does this work. I mean if the prolactinoma is secreting prolactin ( and we all know prolactin increases Dopamine synthesis) how does the drug dopamine stop the growth when the prolactin induced dopamine could not??

 

[hanky1982]

question about pituitary adenoma?

TX- bromocriptine (DA agonist)---> shrinks tumor

How does this work. I mean if the prolactinoma is secreting prolactin ( and we all know prolactin increases Dopamine synthesis) how does the drug dopamine stop the growth when the prolactin induced dopamine could not??

Read More, spend less time on SDN

🙂

 

[BoneNibbler]

Read More, spend less time on SDN

🙂

You could have just said you don't know.

 

[ZagDoc]

Dopamine tonically INHIBITS prolactin synthesis and secretion via the tuberoinfundibular pathway. Prolactin stimulates dopamine synthesis/secretion in this pathway to fulfill the classic endocrine negative feedback. Just like TSH/T3. Higher prolactin -> Higher Dopamine -> Lower Prolactin.

If you have a pituitary adenoma, it had lost its negative feedback regulation since its a neoplasm (not that the cells secrete too much prolactin. It's that there's too many cells for the natural feedback to inhibit). So, even though the high prolactin levels are inducing dopamine synthesis, they have no substantial effect on the tumor. Like throwing rocks at a brick wall. However, if you exogenously add a dopamine agonist like bromocriptine, you REPRESS prolactin synthesis/release. The natural negative feedback has no bearing here because the levels you use of bromocriptine are well above physiologic. But by using such levels of dopamine agonism, you can overcome the autonomy of the prolactinoma. Like a wrecking ball against a brick wall. This causes atrophy of the pituitary adenoma, since it loses function.

 

[BoneNibbler]

Dopamine tonically INHIBITS prolactin synthesis and secretion via the tuberoinfundibular pathway. Prolactin stimulates dopamine synthesis/secretion in this pathway to fulfill the classic endocrine negative feedback. Just like TSH/T3. Higher prolactin -> Higher Dopamine -> Lower Prolactin.

If you have a pituitary adenoma, it had lost its negative feedback regulation since its a neoplasm (not that the cells secrete too much prolactin. It's that there's too many cells for the natural feedback to inhibit). So, even though the high prolactin levels are inducing dopamine synthesis, they have no substantial effect on the tumor. Like throwing rocks at a brick wall. However, if you exogenously add a dopamine agonist like bromocriptine, you REPRESS prolactin synthesis/release. The natural negative feedback has no bearing here because the levels you use of bromocriptine are well above physiologic. But by using such levels of dopamine agonism, you can overcome the autonomy of the prolactinoma. Like a wrecking ball against a brick wall. This causes atrophy of the pituitary adenoma, since it loses function.

Thanks. I didn't know that bromocriptine was at supra-physiologic doses!

And so I guess my real question should have been.........."how does bromocriptine overcome the autonomy of the tumor?"

 

[Tristy]

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[ZagDoc]

Thanks. I didn't know that bromocriptine was at supra-physiologic doses!

And so I guess my real question should have been.........."how does bromocriptine overcome the autonomy of the tumor?"

Pretty much every drug you use is at supra-physiologic doses.

Think of a vial of food red coloring. You add that vial to a glass of water, its going to turn the water red. You add that vial to a swimming pool, its not going to do much. Physiologic dopamine is like a vial of food coloring. It'll turn a glass of water (a normal sized adenohypophysis) red... aka inhibit normal prolactin synthesis/secretion. However, its not going to do much to a swimming pool of water (a pituitary adenoma). However, if you add a 42 gallon drum of red food coloring (Bromocriptine where you swamp the pituitary cells with dopamine agonism), it'll turn the swimming pool red. A pituitary adenoma is a well-differentiated neoplasm. It retains the negative feedback cellular machinary to turn off prolactin expression. It's just that without drugs there's too much water and not enough food coloring to do anything. You're just accentuating the natural feedback mechanism with the drug.

 

[BoneNibbler]

Pretty much every drug you use is at supra-physiologic doses.

Think of a vial of food red coloring. You add that vial to a glass of water, its going to turn the water red. You add that vial to a swimming pool, its not going to do much. Physiologic dopamine is like a vial of food coloring. It'll turn a glass of water (a normal sized adenohypophysis) red... aka inhibit normal prolactin synthesis/secretion. However, its not going to do much to a swimming pool of water (a pituitary adenoma). However, if you add a 42 gallon drum of red food coloring (Bromocriptine where you swamp the pituitary cells with dopamine agonism), it'll turn the swimming pool red. A pituitary adenoma is a well-differentiated neoplasm. It retains the negative feedback cellular machinary to turn off prolactin expression. It's just that without drugs there's too much water and not enough food coloring to do anything. You're just accentuating the natural feedback mechanism with the drug.

Thanks for taking the time to explain. I curse you with good luck on your boards.😀

So then bromocriptine also works via the same D2-receptor?

 

[ZagDoc]

Yup, which remember is linked to a Gi protein. So bromocriptine agonism is going to decrease cAMP in the cells and shut off the prolactin synthesis/secretion pathway.

 

[thethom]

Pretty much every drug you use is at supra-physiologic doses.

Think of a vial of food red coloring. You add that vial to a glass of water, its going to turn the water red. You add that vial to a swimming pool, its not going to do much. Physiologic dopamine is like a vial of food coloring. It'll turn a glass of water (a normal sized adenohypophysis) red... aka inhibit normal prolactin synthesis/secretion. However, its not going to do much to a swimming pool of water (a pituitary adenoma). However, if you add a 42 gallon drum of red food coloring (Bromocriptine where you swamp the pituitary cells with dopamine agonism), it'll turn the swimming pool red. A pituitary adenoma is a well-differentiated neoplasm. It retains the negative feedback cellular machinary to turn off prolactin expression. It's just that without drugs there's too much water and not enough food coloring to do anything. You're just accentuating the natural feedback mechanism with the drug.

Nice explanation!

 

[Deferoxamine]

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