Clock gene necessary for implantation

Endocrinologists are aware of the circadian clock since it determines the release of many hormone likewise cortisol in a daily rhythm. There are other rhythmic hormone releases not dependent on the circadian clock, for example the prolactin release in a circannual fashion, or faster pulses for hormones of the pituitary with one to three hours pulse lengths.

In short, the circadion clock is found in the supraoptic nucleus of the hypothalamus and concists of the RNAs and proteins Per, BMAL, Clock, and cryptochrome(s). These are generated and inactivated in a way that autonomously repeats about every 24 hours. It can also adjust to a light-dark cycle.

What is new in a paper by Liu et al. from the Bradfield labaratory at the Univ. of Wisconsin in PNAS is that steroidogenesis — the synthesis of steroids –is coupled to the clock protein BMAL-1. They show that female mice which fail to express the BMAL protein in steroidogenic cells are not capable to implant an fertilized egg into the uterus and fail to generate progeny. When they transplant one normal uterus into these animals  by exchanging one defective with the normal one, these mice will again produce offspring. The defect can, in addition, be rescued by soluble progesterone which shows that progesterone is a determining factor in nidation/implantation.

These experiments are nicely done. The conclusion, however, that  the hormone production in the ovar is decisive is too far fetched: They have eliminated the entire steroidogenesis in these mice,  therefore the only hormone producing organ of the rescued animals is the transplanted normal ovar. Progestone or other steroid hormones being soluble and acting far away from their place of synthesis could under normal conditions be generated in the adrenal or somewhere else as well. The ovar is by far not the only organ with progesterone synthesis. It will be difficult to answer the question whether the ovar’s progesterone synthesis is required for implantation, since a block in the progesteron synthesis will likely block androgen, estrogen and corticoid synthesis. You would need the 3ß-hydroxysteroid dehydrogenase 1 inactive only in the ovar. And still the animal needs androstendione substitution to allow ongoing testosterone and estrone and thus estradiol synthesis.

Worth to read!

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