For a long time, the melanocortin system was basically thought to control the color of skin and hair. It still does, and many redheads are redheaded due to polymorphisms in one of the melanocortin receptors.
Fast forward to 2015: to make a long story short, melanocortins are HUGE players in circadian biology.
Brief background (also see figure above):
Fed state -> high leptin -> a-MSH -> MC4R (the receptor for a-MSH) = satiety, energy production, fertility, etc.
Fasted state -> low leptin -> AgRP blocks MC4R = hunger, energy conservation, etc.
MC4R polymorphisms in humans are associated with obesity. Melanotan II causes skin darkening (marketed as “photoprotection” [no bueno, imo]), enhanced libido, and appetite suppression.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, fertility, insulin, melatonin, sleep, Sun
Tagged carbs, circadian rhythm, diabetes, diet, insulin, melatonin
It is known. Carbohydrate restriction improves (lowers) testosterone in women with PCOS. It works for men, too… but by “works” I mean “increases.”
Decrease of serum total and free testosterone during a low-fat high fibre diet (Hamalainen et al., 1982)
Intervention pseudo-crossover study: 30 healthy Finnish men in their 40’s were studied on their habitual high fat diet (40% fat), then put on a low-fat (25%) high fibre diet for 6 weeks, then switched back to high fat. The high fat diet was also higher in saturates, P:S ratio 0.15 vs. 1.25.
Free testosterone levels declined on the low fat diet, but they recovered after 6 weeks of going back to their high [saturated] fat dieting (p < 0.01).
Some observational data: Testosterone and cortisol in relationship to dietary nutrients and resistance exercise (Volek et al., 1997)
…fat, and in particular saturated fat, is associated with increased testosterone levels [in men]:
Posted in Advanced nutrition, clamp, diet, Dietary fat, fertility, insulin, sex, testosterone
Tagged calories, carbohydrates, carbs, diet, fat, insulin, testosterone
There are enough connections here to suggest it’s an interesting rabbit hole. Besides the effects of ARBs & desmopressin on mood and cognition, blood pressure regulation is not interesting <– fact. But if it ties into fertility, circadian biology, and seasonal changes in how we should be doing things…
Way back in 1998 when I was graduating high school, Murphy and colleagues were screwing with “light-entrainable” and “food-entrainable” oscillators of circadian rhythmicity (1998). They did this in two lines of rats, one with intact vasopressin signaling and one without. With little mechanistic work, they showed vasopressin mediates circadian effects driven by light; and rats without vasopressin were more entrainable by meal timing. N.B. in addition to the posterior pituitary, vasopressin is also found in the famous circadian light-regulated SCN neurons (Rosving 2010).
While it is speculated to play a role in social behaviors and sexual motivation, vasopressin is primarily known for its anti-hypotensive effects. When plasma volume drops, vasopressin is secreted to decrease urinary water loss and increase blood pressure. This is antagonized by alcohol, which is thought to be one reason why alcohol can dehydrate you.
Posted in Advanced nutrition, angiotensin, circadian, fertility, melatonin, sex, vasopressin, wine
Tagged angiotensin, circadian rhythm, fertility, vasopressin
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:
Posted in circadian, Dopamine, fertility, sex
Tagged calories proper, circadian rhythm, dopamine, energy balance, fertility, kisspeptin, Paleo, prolactin, thyroid
I’ve adapted much of this chart from Howell-Skalla (2002) and Tsubota (1998).
Canadian polar bears: bona fide seasonal breeders.
The light cycle increases until June, then decreases until December. Melatonin goes in the exact opposite direction. Testosterone peaks around the onset of breeding season (springtime, April/May), coinciding with LH (as expected). There is also a lot of bear-on-bear violence at this time due to: 1) testosterone-induced aggression; and 2) the high female:male ratio –-> females rear their cubs and are thus out of the game for about 3 years, but males like to breed every year.
Females followed a similar pattern, with estrogen peaking around breeding season and prolactin following the light cycle.
The authors mentioned that prolactin levels mirrored day length, and according to Wiley this would be the prolactin peak that normally occurs when you’re sleeping, but has spilled over into the daytime due to short sleep / long light cycle… not total prolactin levels (24h AUC?), which should be highest in winter (see below).
Posted in Advanced nutrition, Bromocriptine, circadian, Dopamine, fertility, sex
Tagged circadian, dopamine, light, melatonin, Paleo, prolactin, sex