Estradiol And Testosterone Have Opposite Effects On Microtubule Polymerization

[Such_Saturation]

Estradiol and testosterone have opposite effects on microtubule polymerization.

Click Orch OR in the signature below for an interesting hypothesis about microtubules and consciousness.

 

[Travis]

Nice find. They also seem to have opposing effects on the myelination over microtubules to form nerves. Progesterone and pregnenolone are actually the primary constituents of myelin, and testosterone increases nerve growth through upregulating neuritin.

This is most likely why progesterone has been shown to increase myelin—because it is myelin. Nonetheless, you find whole articles describing the theoretical effects of progesterone on its receptor—desptite!

"These observations imply that progesterone binds to progesterone receptors in the Schwann cell cytoplasm or nucleus, although further investigation is required since progesterone receptor was not detected in mouse sciatic nerves (I. Jung-Testas and H. Koenig, unpublished)." ―Koenig

This doesn't stop the others from writing entire review articles without mentioning this fact. You have to give Koenig some credit for at least mentioning more than the others, and that progesterone receptors weren't found in the mouse nerve—which can remyelinate just fine—which is something most authors seem to painfully avoid.

[Reprinted without permission from: Schumacher, Michael, et al. "Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination." Growth hormone & IGF research 14 (2004): 18-33.]

And for confirmation that the rest of myelin is composed of phospholipids and DHEA sulfate, see below:

• Morfin, Robert, et al. "Neurosteroids: pregnenolone in human sciatic nerves." Proceedings of the National Academy of Sciences89.15 (1992): 6790-6793.

Do the microtubules—the inner nerve—need any help from enzymes or receptors to myelinate? do they need something to attach the progesterone for them?

Apparently not; see below:

• Murakami, Koichi, et al. "Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly." Proceedings of the National Academy of Sciences 97.7 (2000): 3579-3584.

In which it's plainly shown, in vitro, that pregnenolone and progesterone have a very high affinity for microtubules.

Which is why it pains me to see these these prolix reviews including hypothetical ways in which progesterone could "stimulate" myelination, while no time seems to be given to modeling the spontaneous nucleation. Solubility considerations and binding affinities could be all you need to describe this, especially considering the fact that the progesterone receptor has not been detected in mouse sciatic nerve.

Myelin is progesterone, pregnenolone, and DHEA progressively stacked in shells surrounding and insulating the inner microtubule nerve. Both progesterone and pregnenolone have been shown to speed recovery time from nervous injury, and female rats are found to have a thicker myelin sheath.

So in females, the microtubule-inhibiting effect of 2-methoxyestradiol appears to be counteracted by higher progesterone levels. Perhaps additional pregnenolone or progesterone could help form a more stable microtubule network? This could lead to a better long-term memory, but perhaps this would be offset by reduced plasticity?

Not sure; but these two steroids play a big role in the stabilization of microtubule networks, and on the myelination of long-range nerves.

"It remains to be determined whether progesterone acts directly on Schwann cells or if its myelin-stimulating effect is mediated through an axonal signal. An axonal signal is known to be necessary for the initiation of the myelination process (for review, see Salzer, 1995). The hypothetical mechanisms of the stimulatory effect of progesterone on remyelination in lesioned nerves are shown (Fig. 5 [see corny flow chart])." ―Koenig

 

[michael94]

Interesting, both of you

 

[Travis]

‘Furthermore, in progesterone receptor knock-out adult mice, the myelin sheaths around sciatic nerve axons are the same as in wild-type mice (Jung-Testas et al., 1999).’ ―Koenig