Phytoestrogens aid flightless parrot- Soy will still not give men breasts

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Phytoestrogens are simply plant-derived xenoestrogens (mimics of estrogen). They’re abundant in legumes (soy, notably), but also present in many other plants. Despite their presence in certain plants being touted as scary, I’d say they’re pretty misunderstood.

Phytoestrogens help breeding success of kākāpō, the flightless nocturnal parrot

The darling flightless parrot of New Zealand has a struggling population partly because it only breeds once every few years. They seem to only breed during mast years (when plants produce a ton of edible fruit/seeds) and seek out fruit from the native rimu tree, which suggested the birds breeding success may rely on the presence of phytoestrogens found in the native plants. The hypothesis is that kākāpō don’t produce enough estrogen to make a fertile egg but the phytoestrogens act as supplements.qjjo1oz4sopgxokvcjww.jpg

The scientist conducting this study tested the native plants for estrogenic content and found high levels of phytoestrogens. They looked at the ligand binding region of the progesterone receptor, the androgen receptor, the estrogen receptor 1, and estrogen receptor 2 in four native parrot species, and non-native parrots and compared them with chicken receptors. They found that in most receptors there was more then 90% homology except in the estrogen 1 receptor. Parrot estrogen receptors are actually genetically different, containing an extra 8 amino acids in the hormone binding region, which changes the binding strength to estrogen.

Soy probably pretty good for you

Screen Shot 2017-07-30 at 11.12.05 AM.pngActive compounds of soy include isoflavones- daidzein, genistein, and glycitein. They act as phytoestrogens, a word which seems to frighten some people. A popular belief amongst anti-soy people is that men who ingest too much soy are going to re-enter puberty and turn into estrogen-filled feminized men (heaven forbid).

But this is not really what’s going on.

Phytoestrogens are structurally similar to estradiol so they have the ability to cause either estrogenic or antiestrogenic effects by blocking estrogen receptors. Phytoestrogens have weak estrogen activity in your body, so they may also bind weakly to estrogen receptors. They don’t displace estrogen, they supplement it.

Plants like soy have evolved phytoestrogens to protect from harmful microbes and to help form nitrogen-fixing root nodules.

So the expectation is that they act like antiestrogens in high estrogen concentration environments, and act like estrogen in low estrogen environments.

There are actually a lot of different estrogen receptors in the human body so the same chemical could be and agonist on one estrogen receptor type and an antagonist on another. So the phytoestrogens in plants could trigger an increase or decrease in endogenous estrogen through feedback loops.

It is almost certainly a serious oversimplification to say phytoestrogens are estrogen mimetics. Lots of compounds have partial agonist activity, meaning that at one concentration they are agonists and at a different concentration they are antagonists. It is possible they could affect the different receptors differently.

Reasons to even get excited over Phytoestrogens

Certain hormonal cancer (uterine, prostate, breast etc.) risks could possibly be lowered with phytoestrogen consumption. If they do actually compete with and block estrogen (an antagonist) at estrogen receptors in the breasts, cervix, or uterus, or if they depress estrogen production, they could tend to inhibit estrogen dependent tumors.

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Phytoestrogens may even provide some sort of benefit to women undergoing menopause and experiencing hot flashes, and post-menopausal women at risk for developing osteoporosis and issues in cognitive function which can sometimes be experienced due to dramatic hormone changes.

If phytoestrogens are agonists at estrogen receptors on osteoblasts and osteoclasts they will help reduce osteoporosis. These estrogen receptors are quite different from the receptors on breast tissue.

From a meta analysis on the effects of isoflavones on bone mineral density in menopausal women: “Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90 mg/day of isoflavones are consumed. And soy isoflavone consumption for 6 months can be enough to exert beneficial effects on bone in menopausal women.”

Soy phytoestrogens are associated with much less negative effects than synthetic endocrine disruptors. And while results of most of these soy studies are dubious—varying with age, level of consumption, and the composition of the individual’s intestinal microflora, soy studies are just as well supported as pretty much any other “eat/drink more of (vegetable, tea, “superfood” etc) and (some health benefit) happens” claims.

While most people tend to be skeptical of simply ingesting a plant and deriving benefits (especially when they are comparing the plant to the highly powerful and concentrated drugs we’ve developed), underestimating and understudying plants has brought about, and continues to bring about, death and illness to plenty of people. So maybe it provides small benefits, but at the very least research does seem to have debunked the myth that soy is dangerous for people.

Constituents of soy if you’re still worried

 

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  • Protein
  • Oil- large amounts of polyunsaturated fatty acids (i.e. linoleic acid (omega 3))
  • Carbohydrates
  • Vitamins and minerals- K, P, Ca, Mg, Fe, B-Vitamins, antioxidants
  • Isoflavones
  • Phytosterols– Disogenin –sterol- is converted to progesterone in body
  • Phospholipids
  • Saponins*- being looked at especially
  • Ferritins- Soybean is a good source of iron
  • Phytic acid
  • Glyceollins- antiestrogen activity
  • Lunasin- peptide

Sources:

  1. Unique oestrogen receptor ligand-binding domain sequence of native parrots: a possible link between phytoestrogens and breeding success. Catherine E. J. Davis A , Adrian H. Bibby A , Kevin M. Buckley A , Kenneth P. McNatty A and Janet L. Pitman. 11 July 2017.
  2. 2014 Jul 7. Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis. Cheng PF1, Chen JJ, Zhou XY, Ren YF, Huang W, Zhou JJ, Xie P.
  3. 2003 Jan-Feb. Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: a literature review. Hermansen K1, Dinesen B, Hoie LH, Morgenstern E, Gruenwald J. .
  4. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. Myung SK, Ju W, Choi HJ, Kim SC; Korean Meta-Analysis (KORMA) Study Group.
  5. Soy intake and cancer risk: a review of the in vitro and in vivo data. Messina MJ1, Persky V, Setchell KD, Barnes S.
  6. 2014 May 28. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: A systematic review. Thomas Ismail, Taylor-Swanson Cray, Schnall, Mitchell, Woods
  7. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Hamilton-Reeves JM1, Vazquez G, Duval SJ, Phipps WR, Kurzer MS, Messina MJ.
  8. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Ma DF1, Qin LQ, Wang PY, Katoh R.
  9. Soy isoflavones for osteoporosis: an evidence-based approach. Taku K1, Melby MK, Nishi N, Omori T, Kurzer MS.
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Platypus venom- weird and unique, as expected

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“Do you think God gets stoned? I think so — look at the platypus.”

-Robin Williams

Venom isn’t very special in the animal kingdom, but our anthropocentric mindsets tend to focus more on large mammals than anything else, so to us it seems pretty mystical. Only a dozen or so mammals deliver venom, almost all of which deliver it via a bite for defense or predation. The platypus is unique in that it is so far the only animal known to use venom for a purpose other than defense or predation.

Only the male platypus has venom. And the male platypus only seems to have potent venom seasonally. The season when they have a lot of venom is unsurprisingly mating season, as the males actually use their venom, injected via venomous spurs on their hind legs, for intraspecific competition with other platypus males to keep territories and mates. While technically the echidna has venom, it can’t erect it’s spurs, and simply excretes a milky secretion.

platypus-spur-png.pngTheir venom, though nonlethal, causes excruciating pain for hours or days and is essentially nonresponsive to morphine. Only nerve-blocking agents (or antivenom) can provide relief.

A 2010 study found 83 peptides in platypus venom, many of which resemble venom genes from snakes, sea stars, and spiders. The platypus and reptiles have independently co-opted the same genes for venom usage making the platypus venom a cool example of molecular convergent evolution.

And just so the monotremes can continue to follow their pattern of general nonconformity and being surprisingly different from each other, the echidna venom gland transcriptome looks very different from the platypus one. You can read this post on their weird sex chromosomes for more.

The venom induces Ca2+ influx in cells, which results in neurotransmitter release. Defensin-Like peptides (defensins being immune proteins that usually defend the host from microbes), C-type natriuretic peptides (OvCNPs), nerve growth factor (OvNGF), and hyaluronidase have also been found. These peptides cause muscle relaxation, inflammation by promoting histamine release, and form ion channels in the lipid membranes of cells. The venom also contains a D-amino acid (as opposed to just all L-amino acids, which is the isomer previously thought to be the only conformation manufactured by cells).

First venomous animals were mammals
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Artist interpretation of Euchambersia mirabilis

The platypus having venom and laying eggs isn’t even that weird, as it seems to be that that was the norm for the ancestors of mammals. Euchambersia mirabilis, a therocephalian therapsid from the end of the Permian (~255 mya), which were some of the “almost-mammals” (the term “mammal-like reptile” is horribly outdated and silly but for some reason people still use it), was determined to have venom glands. Venom glands which appeared way before snakes and lizards evolved them, and actually millions of years before any snakes even existed.

bk9781849736633-00001-f1_hi-resSo while venom in mammals is very rare now, it may actually be an ancestral characteristic. Venom relatively expensive to have as it requires some method of injection into another animal, a gland, and then the making of proteins. It’s also suspected to be expensive because the loss of venom in animals that are no longer under pressure to produce any, is very common. Venom has a weak phylogenetic signal—similar types of venom are not necessarily found near each other on a phylogenetic tree, so genetically it seems not very “difficult” for various venoms to arise.

Monotreme venom as diabetes treatment?

The hormone, glucagon-like peptide-1 (GLP-1), is secreted in the gut, stimulating the release of insulin to lower blood glucose. But GLP-1 typically degrades within minutes in humans.

People with type 2 diabetes can’t maintain a normal blood sugar balance, but maybe they could if they had a less rapidly degrading GLP-1.

However in the platypus, there’s conflicting functions of the GLP-1. Not only is it a regulator of blood glucose in the gut, it is also in their venom. This conflict between the two different functions has resulted in the evolution of a dramatically changed GLP-1 system. GLP-1 in monotremes is resistant to the rapid degradation that occurs in other animals, and degrades by a completely different mechanism.

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GLP-1 and diabetes relationship

The function of GLP-1 in the venom seems to have resulted in the evolution of a stable form of GLP-1 in monotremes. Stable GLP-1 molecules can potentially be used as a type 2 diabetes treatment.

Both platypus and echidnas have evolved the same long-lasting form of the hormone GLP-1 despite echidnas not having spurs.

 

Sources:

  1. Kita, Masaki, David Stc. Black, Osamu Ohno, Kaoru Yamada, Hideo Kigoshi, and Daisuke Uemura. “Duck-Billed Platypus Venom Peptides Induce Ca2 Influx in Neuroblastoma Cells.” Journal of the American Chemical Society50 (2009)
  2. Enkhjargal Tsend-Ayush, Chuan He, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank Grutzner. Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions. Scientific Reports, 2016
  3. Julien Benoit, Luke A. Norton, Paul R. Manger, Bruce S. Rubidge. Reappraisal of the envenoming capacity of Euchambersia mirabilis (Therapsida, Therocephalia) using μCT-scanning techniques. PLOS ONE, 2017