Saturday, October 8, 2011

Estrogen for the Male & Female Physical Culturist? Differential Health Effects in Men and Women. Plus, Estrogen's Role in Satellite Cell Recruitment.

Image 1: Should HE take HER estrogen birth control pills? Or should even she abstain from any exogenous estradiol?
(img free-press-release.com)
Since the earliest research into this topic goes back into the mid 1999s, you will probably have heard about the beneficial effects estrogen has on Alzheimer's (Simpkins. 1997), haven't you? Those headlines along the lines of "Estrogen is the reason why women don't get Alzheimer's as often as men" or "Estrogen protects women from cognitive decline". Now, does that mean that both male and female bodybuilders and fitness athletes should finally give in and stop controlling their estrogen levels in order to get / stay as lean and ripped as possible? Well, a recent study that has been published electronically, ahead of print, in the journal Life Sciences could well shed some light on the question whether for whom of you the down-side to a "no-bloat low estrogen" physique could in fact turn out to be Alzheimer's.

In their study a group of scientists from the Chiang Mai University in Thailand investigated the effects of 50µg/kg subcutaneously injected estrogen for 30 days on the negative impact a "high fat" (I am not tiring of repeating myself that this diet is not only high (60%) in fat and carbohydrates and has 33% more calories on a gram per gram base) had on a group of 40 male and female Wistar rats (Pratchaylsakul. 2011), to test the hypothesis that
the administration of estrogen in both male and female rats can reverse the impairment of
both insulin-induced LTD [in other words: neuronal insulin resistance] in the hippocampus and neuronal insulin signaling caused by a 12-week HF diet consumption.
And as in every good study, W. Pratchayasakul et al. were able to disprove their hypothesis - at least partly. While the desired effects on neuronal insulin signaling did occur in the female mice, similar changes could not be observed in their male peers.
Figure 1: Changes in plasma (pg/ml) and brain (pg/mg) estrogen levels upon administration of 50µg/kg 1 to 40 male and 40 female on different dietary regimens for 30 days (data based on Pratchaylsakul. 2011)
Now, as you can see in the data in figure 1, this effect is not really "sex-specific", in the sense that estrogen would be good for female rat brains and bad for male rat brains, but it is rather the result of an almost paradoxical -14% reduction in brain estrogen levels in the high fat fed female rats who received the 50µg/kg 17-β estradiol. That this differential reaction yet is not the (only) underlying mechanism can yet be seen from the fact that there was a similar, yet statistically non-significant -7% reduction in brain estrogen in the high fat fed male rats, who - this can be seen from the changes in glucose and fatty acid metabolism I plotted in figure 2 - did not benefit to the same extend from supplemental estrogen as their female companions.
Figure 2: Relative improvements in glucose and fatty acid metabolism in rats on a high fat diet after administration of 70µg/kg 17-β estradiol (data calculated based on Pratchaylsakul. 2011)
Nevertheless, even in the male rats, the higher plasma estrogen level (+450%) was not without purportedly beneficial effects on markers of insulin resistance (HOMA-IR, insulin p<0.05 from control) and fatty acid metabolism. Now, before you consider taking some of the estrogen based oral contraceptives of your significant others, I suggest you better look at the price the male rats had to pay for these mediocre improvements in peripheral insulin resistance (cf. figure 3).
Figure 3: Modularory effects of 70µg/kg 17-β estradiol on increases in body weight and visceral fat mass in HFD fed rats compared to rats receiving a normal diet (data calculated based on Pratchaylsakul. 2011)
As you can see the body fat gain of the the male rats literally exploded (+132% over normal diet) when, in addition to the already fattening (+95% over normal diet) high fat diet they also received their daily dose of estrogen. On the contrary, in female rats who turned out to be much more susceptible to high fat diet induced body fat gains, 17-β estradiol reduced the increase in body fatness from +271% in the unsupplemented high-fat group to "only" +125% in the female rats who received 17-β estradiol treatment.
Illustration 1: Damaged muscle tissue will recruit quiescent satellite cells to regenerate the myofiber (img. Scime 2009)
Estrogen? Wait a minute... wasn't there a connection between estrogen, satellite cells and muscular hypertrophy? There are indeed a series of studies which suggest that estrogen does play a major role in the muscular adaption processes to exercise. Estrogen in and out of itself is a strong antioxidant, with properties similar to vitamin E (Subbiah. 1993). It is also known to stabilize cell membranes and thus it is not really surprising that Amelink et al. report a direct inverse relationship between estrogen supplementation and CK release [marker of cellular damage] from muscles of both male and female rats (Amelink. 1990). This may also explain differential effects on muscle damage observerd by Komulainen et al. in a study where male and female rats were exposed to eccentrically biased downhill running and only the male rats suffered from damage to the microarchitecture of the muscle (Komulainen. 1999). Moreover, estrogen increases the expression of HSP-70, one of the heat shock proteins which are expressed as a reaction to acute stressors and "act to attenuate further protein disruption when a subsequent stress such as exercise is again introduced" (Tiidus. 2011).

Now, more importantly, estrogen will also enhance 24 and 72 hours post-exercise muscle satellite cell activation and proliferation (in overiectomized rats, Enns. 2010), which is actually counterintuitive, because estrogen also blocks macrophage infiltration, which has been implicated in satellite cell activation and muscle repair, as well. The beneficial effects on estrogen on satellite cell activation is however mediated directly via estrogen receptors on skeletal muscle (Igbal .2008). As possible underlying mechanisms, Enns et al. list
  • insulin-like growth factor-1 (IGF-1) signalling, 
  • NO signalling and 
  • signalling via the  phospho-inositide-3 kinase/protein kinase B (PI3K/Akt) pathways
All these results have yet to be treated with some caution, because most of the data comes from ovariectomized rats and thus applies only (if at all) to post-menopausal women. This is specifically true for the benefits of "supplemental" exogenous estrogens, of which I doubt that it would promote muscle gains in either men or women (with normal hormone levels).
After all, high estradiol will thus rightly remain among every male bodybuilder's list of chief villains - for the female bodybuilders and figure competitors out there, this could yet be different - after all the beneficial effects especially in terms of neuronal glucose metabolism, which were not be observed in the male rats, could come handy, yet even then, the increase in visceral fat, which was also present in the female rats on a normal diet (+31%!) is a trade-off I am not so sure it would be worth paying.