It’s paleo: Hypothyroidism impairs reproductive success in bitches.

Kisspeptin was discovered in Hershey, Pennsylvania, and was named after Hershey’s Kisses.  It has 776 pubmed citations going back to 2001, and may (or may not) play a key part integrating circannual reproduction patterns and seasonal thyroid function.

Kisspeptin was originally identified as a protein that inhibited breast cancer and melanoma.  This might also provide insight into the WHO’s recent declaration of shift work as a “probable” carcinogen.

Exhibit A. TSH restores a summer phenotype in photoinhibited mammals via the RF-amides RFRP3 and kisspeptin (Klosen 2013)

In this study, TSH infusion in short-day adapted hamsters (who are in winter non-breeding mode) induced summer phenotype & kisspeptin.  It also fattened them up a bit.  These TSH secreting neurons express melatonin receptors, but not those for TRH or T3 (Klosen 2002), so it is said to go something like this:Kisspeptin feedback diagram

I don’t think this is the same TSH that is involved in regulating thyroid proper, because those TSH neurons would express TRH & T3 receptors.  However, melatonin suppresses TSH (which is thought to mediate the slight reduction in body temperature at night), and in this human study (Mazzoccoli et al., 2004), TSH increased in the blood prior to melatonin onset, but started to go down when melatonin levels started to get up there:TSH and melatonin

So perhaps it’s a different set of TSH neurons.  However, T3 administration does the same thing –> enhances kisspeptin and testicular growth [in hamsters] (Henson et al., 2013).  So maybe not.


Melatonin inhibits kisspeptin in short photoperiods (Simonneaux & Ancel, 2012), presumably to reduce the odds of winter conception which would result in autumn parturition.  Melatonin injections also induce winter-like infertility in these animals.

The Neurobiology of Circadian Timing <– I suspect  has all the answers.

Aside (speculative).  Hamsters and many birds, like our theoretical paleo ancestors, are long day breeders: spring conception leads to spring births (Ikegame & Yoshimura, 2013); in humans, summer conception leads to spring births.  Spring was historically [theoretically] a good time to have a baby.  Short day breeders (bun in the oven ~6 months), like some sheep, deer, and goats prefer autumn conception which similarly leads to spring births.  The marked species-dependent variations does seem to complicate things, given that the paucity of human data on kisspeptins and the like.  For what it’s worth, humans with a mutated kisspeptin receptor are infertile (Roux 2003).

With regard to fertility: Kisspeptin > photoperiod.  In spring, TSH-induced kisspeptin expression promotes fertility; in winter, melatonin inhibits both.


Thyroid function is critical to fertility.  Iodine supplementation is thought to improve breeding success in pandas (Milewski & Dierenfeld, 2012), and hypothyroidism markedly impairs reproductive success in bitches (plz click link) – this would be “winter;” paleo/Wiley/seasonal winter.  And kisspeptin appears to be the messenger.  Thyroid activates it in summer, and melatonin inhibits it in winter.  What could make this story interesting?  Something else that affects kisspeptin.  Yeah, that’d be cool.  End.

calories proper

Remember when I promised I wouldn’t start wearing a tin foil hat?  That’s still true, but I might start wearing a pair of hot blue-blocker sunglasses at dusk.  Even inside my apartment.

“I think my mask of sanity is about to slip” –Patrick Bateman

I used to draw the line at a foil cap.  Now the line has been redrawn to wearing hot blue-blockers at indoor public places.  Like the grocery store, or a pub (where I’d probably get my ass kicked for it by a gang of mulleted rednecks).  I really hope that line doesn’t get redrawn.

he gets away with it.

he gets away with it.

 

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  • http://itsthewooo.blogspot.com/ Jane Plain (Woo)

    This was fantastic; It’s well known hypothyroidism promotes anovulation and infertility but I never bothered to research the exact mechanism… in my mind, it was just this black box where I assumed cellular energy deprivation just magically abra cadabra somehow terminated an entire endocrine axis from working.

    Now I know how this happens 😉
    T3 suppression via organ level pathology or functional inhibition of TSH (as occurs in starvation, light deprivation/late autumn & winter, or other unfavorable environment conditions) will prevent kisspeptin neurons from activating GnRH normally. Obviously this would arrest the hypothalamic pituitary gonadal axis.
    This is rather similar to how leptin promotes infertility; meaning, it doesn’t actively *cause* infertility but fertility is impossible without it. Leptin deficiency also independently reduces TSH (but, leptin is required / affects fertility very directly as well).

    I am considering getting the light blocking glasses as physically speaking I feel like my entire body is assaulted if I have to go to the bathroom at “night” (which is like, noon :( ) .

    I had always assumed skin was able to suppress melatonin and presumably phase shift circadian rhythms…but this finding is controversial it seems. Previously I never bothered to block the light from my eyes because I figured WUTS THE POINT MY TRAITOR SKIN WILL GET ME ANYWAY.

    I totally need those glasses.

    • http://www.caloriesproper.com/ William Lagakos

      most of the evidence I’ve seen suggesting skin will betray you (n=3) comes from studies on blind people.
      PMIDs: 8590557 & 7990870
      and this one (light to the back of the knees): 9430592

      But most stuff [I’ve seen] suggests skin won’t do the trick, and this isn’t even including the studies on the actual blue blockers themselves (which seem to be pretty effective).
      PMIDs: 11094143, 10494452,10553954, & 12164253

      on another note, I have this creepy red light in my bathroom. I’ve been told it’s for heat, to reduce the steam and prevent mold… but it really just looks like a horror movie or something. Perhaps I should start using it at night. Or I’ll sport the blue blockers I just ordered :)

      .

  • Michael

    Does Seth Roberts get away with it?

    http://vimeo.com/29391910

    • http://www.caloriesproper.com/ William Lagakos

      Ha! thanks for the link. Those are some major Blue Blockers.

  • Michael

    Hi Bill,

    I’m not sure if this has been covered in any of your previous posts, but I just stumbled on this:

    http://fortheloveoflipids.blogspot.com.au/2013/09/food-reward-circadian-rhythm-reset.html

    Very interesting blog, too! Hadn’t seen it before.
    Warning!: does contain the term ‘food reward’. Don’t let that put you off though.

    • http://www.caloriesproper.com/ William Lagakos

      Hi Michael. Thanks for the link, that’s one helluva biohack!