Caffeine By Afrida: Science Round-Up Seconds: Nicotine's Effect on Brain Aromatase & the Consequences, 2D:4D Digit Ratio Predicts Testosterone Response to Sprinting and All the Anti-Obesity & Pro-Brain Effects W/ Just 2 Cups of Coffee per Week?

Wallaby Lachie Turner (left), Greg Inglis (centre) & Jarryd Hayne (Stuff.co.nz) - who would have thought that the relative length of their 2nd and 4th digit could predict their testosterone response after the sprint? Not you? Well, then you got to check out the first of the short-items at the bottom.

Those of you who have listened to yesterday's installment of the SuppVersity Science Round-Up on Super Human Radio, will have realized that the show did - as usual - take a somewhat different direction than originally planned. Before I get to the actual SuppVersity Round-Up Seconds, of which there actually weren't all too many I consider absolutely newsworthy and appropriate for a written format, I thought I would briefly mention the paper on which I based the hypothesis (remember: this is nothing certain) that there may be a link between the calcium-influx into the muscle and the strength and hypertrophy effects of performance enhancing drugs (spec. those with a high anabolic : androgenic effect ratio) - for those of you who may want to follow up on this hypothesis or think Carl and I were just making things up ;-)

The study I refer to shortly after the last break (download the podcast), was conducted by a group of researchers from the Instituto de Ciencias Biomedicas at the Universidad de Chile in Santiago de Chile, dealt with the modulatory effects of testosterone (and aldosterone) on intracellular calcium response in skeletal muscle cell cultures and not the subsequent consequences on contractile force of hypertrophy and could thus only serve as a point of departure for future investigations to either confirm or refute this idea (Estrada. 2010).

Nicotine exposure, brain aromatase and gender-specific implications

With the advent of new technologies, esp. the direct observation of aromatase activity in primate brains (Lidstrom, 1998; Kim, 2009; Biegon, 2010), our understanding of the peripheral effects of certain substances on hormone metabolism, one of the latest such insights pertains to the effects of nicotine exposure on the expression of the aromatase enzyme in the brain.

Figure 1: Effect of nicotine on brain aromatase availability in the female baboon. Representative baseline PET image coregistered with MRI at baseline and following injection of low dose (0.015 mg/kg) or high dose (0.03 mg/kg) nicotine. PET images show averaged frames acquired between 52.5 and 90 min after tracer injection, pseudocolored using the rainbow spectrum, with purple indicating the lowest density and red indicating the highest density of radioactivity (from Biegon, 2010).

In a recently published paper scientists from the Brookhaven National Laboratory Upton in New York did now connect the dots between the previously observed direct inhibitory effects on the central expression of the CYP19a mediated expression of the aromatase enzyme of nicotine and (potentially) other tobacco alkaloids. Thus, Anat Biegon, Nelly Alia-Klein and Joanna S. Fowler are not only able to explain, why women are more susceptible to the addictive effects of the nicotinic acetylcholine receptor agonist, which accumulates in the leaves of several members of the Solanaceae (nightshade) family, than men, but observations such as the early onset of menopause and lower plasma estrogen levels and correspondingly higher osteoporosis risk in female smokers compared to their non-smoking peers, as well (Daniell. 1972; MacMahon. 1982; Nusbaum. 2000; Pant. 2008; Korkor. 2009).

Table 1: Comparison of the effects of nicotine exposure and the effects of an aromatase inhibitor (at different time points in life) on sexual behavior, anxiety and depression, hot flashes, and weight gain in men and women (Biegon. 2012)

The scientists also list a couple of other ascertained side-effects pertaining which are equally important to men and women: The sexual behavior for example has been shown to drop both in response to prenatal, as well as acute nicotine exposure in male mammals - something those of you who happen to have a prescription for an aromatase inhibitor as an adjunct to their TRT regimen and did not hit the sweet spot between too much and too little estrogen, will certainly be aware of. While anecdotal evidence clearly points into that direction the scientific consensus on the negative impact of aromatase inhibitors on male libido in men (not male rodents), is however not yet clear. Personally, I believe this is partly due to the fact that pertinent studies usually deal with subjects who reduce their estrogen levels to normal, which could in fact lead to increased testosterone and DHT level in the absence of any negative side effects on the patients' libido.

If you take a look at the overview in table 1, you will however realize that other effects as the anxiolytic effects of acute nicotine exposure in adult women or the weight loss effect (which is certainly another reason women like to smoke) stand in direct opposition to the hypothesis that the majority of nicotines beneficial and negative side-effects were mediated by its effects on the aromatase enzyme. Fortunately, for most smokers, this appears to apply to the pro-Alzheimer's effects of low brain aromatase (Hiltunen. 2006), as well - at least, if we go by the conflicting results of the latest epidemiological studies, which contradict earlier findings that did even suggest that smokers would have a lower risk of Alzheimer's disease.

Alzheimer's, dementia, etc. are yet only examples of the far reaching effects brain aromatase and its regulation by nicotine and other substances such as aromatase inhibiting drugs, but also all sorts of environmental toxins with endocrine side-effects could have - so you can easily expect more interesting study results in the future.

Other news that did not make it into the show

As I have mentioned in the introduction, we did cover a hell lot of ground, so that most of the other studies are directly related to the luteinizing hormone negative feedback and thus no real "news" - I skipped discussing those, since I though that everyone listening will get the main message and did not want to bore those of you who are not interested in this topic with a show solely on the effects of nutrient deprivation and exercise on the endocrine milieu. But enough of the excuses, there is still more:

Right-left digit ratio (2D:4D) predicts testosterone response to exercise in 79 professional Rubgy players (Kilduff. 2012) - In the analysis, researchers from the Swansea University at the Sports Science, Talbot Building in Singleton Park, Swansea, UK, found that despite significant differences in basal testosterone levels, the 2D:4D ratio, which is generally regarded as an indicator of in-utero androgen exposure was significantly associated with a lower testosterone response to repeated sprint-agility tests in the 25 subjects who participated in the active arm of the study.

Caffeine prevents weight gain and cognitive impairment by high fat diet (Moy. 2012) - This is not news? Just read on, you will soon realize that it is news! Firstly, the scientists from the University of Albany identified an ameliorative effect of caffeine on the diet-induced reduction of hippocampal expression of the brain-derived neurotrophic factor (BDNF) as the underlying mechanism behind it's neuroprotective effect (the same stuff that's also increased by exercise, by the way).

Figure 2: Assuming this is not a mistake in the study caffeine once a week would be enough to boost the BDNF levels of junk-food and normal eaters alike (Moy. 2012)
And secondly, the rodents received only a single, weekly intraperitoneal injection that would be equivalent to ~250mg in a human being (I double checked, the study says: "All animals received either caffeine (20 mg/kg) or saline (volume-matched), i.p., once weekly."; my emphasis in Moy. 2012). If that's not a mistake, chronic caffeine consumption may not even be necessary to see a hell-lot of the anti-diabetes and anti-neurological damage effects of coffee - just 2 cups once per week that's it!

And if you look closely at the data in figure 2 you see that even "normal" people may benefit from this regimen.

Since tomorrow is an official installment of "On Short Notice" due, I will leave you on that flabbergast caffeine study and just remind you that there is - as everyday (guaranteed even on Christmas ;-) tons of interesting new stuff on the SuppVersity Facebook Wall, as well - let's see what we have today:

Insulin has anti-Alzheimer's effect - Yeah you read me right. It reduces the formation of ameliod beta plague (read more)
Yet more plant extracts with natural anti-cancer activity: Chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L known in TCM as Rui Xiang Lang D (read more)
Want to father a Nobel Laureate and in your early to late 30s? Than its about time you procreate! Study finds U-shaped curve for father's age and intellectual abilities of the offspring peaking at 32-37 years or so (read more)
...plus the rest I did not mention (read all)

I guess with the podcast to listen to and some food for thought on once-weekly caffeine administration (on a side note, injecting into the intraperitoneal cavity is, for most substances, only minimally different from oral ingestion and done only to assure that the animals don't spit whatever you want them to ingest back out) you will survive the next couple of hours until the facebook news will receive another update and the next installment of "On Short Notice" is going to be published? If not, complain in the comment area ;-)

References:

Biegon A, Kim SW, Alexoff DL, Jayne M, Carter P, Hubbard B, King P, Logan J, Muench L, Pareto D, Schlyer D, Shea C, Telang F, Wang GJ, Xu Y, Fowler JS. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole. Synapse. 2010 Nov; 64(11):801-7.
Biegon A, Alia-Klein N, Fowler JS. Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain. Front Pharmacol. 2012;3:185.
Daniell HW. Osteoporosis and smoking. JAMA. 1972 Jul 31;221(5):509.
Estrada M, Liberona JL, Miranda M, Jaimovich E. Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures. Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E132-9.
Hiltunen M, Iivonen S, Soininen H. Aromatase enzyme and Alzheimer's disease. Minerva Endocrinol. 2006 Mar;31(1):61-73.
Korkor AB, Eastwood D, Bretzmann C. Effects of gender, alcohol, smoking, and dairy consumption on bone mass in Wisconsin adolescents. WMJ. 2009 Jul;108(4):181-8.
MacMahon B, Trichopoulos D, Cole P, Brown J. Cigarette smoking and urinary estrogens. N Engl J Med. 1982 Oct 21;307(17):1062-5.
Moy GA, McNay EC. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF. Physiol Behav. 2012 Dec 6.
Nusbaum ML, Gordon M, Nusbaum D, McCarthy MA, Vasilakis D. Smoke alarm: a review of the clinical impact of smoking on women. Prim Care Update Ob Gyns. 2000 Sep 1;7(5):207-214.
Pant S, Shapiro CL. Aromatase inhibitor-associated bone loss: clinical considerations. Drugs. 2008;68(18):2591-600.
Roselli CE, Abdelgadir SE, Ronnekleiv OK, Klosterman SA. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol. Reprod. 1998; 58, 79–87.
Roselli CE, Resko JA. Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J. Steroid Biochem. Mol. Biol. 2001; 79, 247–253.