[Lotus]

Hi LisaM, thanks for the reminder. Sometimes my chemo meds make me have some senior moments. The science behind what I'm going to explain is complex… However, I'm going to give my own take in layman's terms which is still a little complicated. 

Estradiol, (17beta-estradiol) binds highly to bovine endometrial and uterine tissues… but is more effective at lower dosages. There are approximately 507 binding sites per nucleus in mature heifers. If anyone remembers I mentioned the importance of knowing when (age) the heifers are harvested as immature calves have no binding sites. So, basically, BO doesn't seem to have competitive binding from weaker hormones (e.g. testosterone or progesterone, and more than likely any herbal supplements) Which means (imho) that BO and Estradiol-(17beta estradiol) work synergistically together. The following statements below are from the study (PDF version). happy reading. 
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We note that the in vitro high affinity site is absent in immature calves and also in mature heifers during the late metestrus and the proestrus stages of the estrous cycle. During diestrus the blood level of estradiol is low (42) and the tissue is prepared to respond, and thus the availability of open sites 011 the nucleus seems reasonable. During proestrus the blood level of estradiol is rising rapidly, the tissue is visibly responding and presumably the sites are unavailable because they are blocked by the bound endogenous hormone. As expected the number of sites increases through estrus where the hormone has completed its stimulation of endometrial proliferation, and the blood level of estrogen is declining. However, during early metestrus 
and late metestrus when the blood level of estradiol is quite low, the number of nuclear sites become vanishingly small, even 
though it is unlikely that at this stage of the cycle that the sites would be blocked by endogenous hormone. 

Estradiol-17/beta causes cell proliferation in endometrial tissue approximately 48 hours after blood levels of the steroid rise 
during the estrous cycle (1). Prior to cell division there is an initial increase in ribosomal RNA synthesis (2) and 24 hours 
later an increase in DNA synthesis (3). It has been proposed that the hormone itself mediates at least.


The Binding of Estradiol-17β to the Bovine Endometrial Nuclear Membrane

The interaction of estradiol-17β with mature bovine endometrial tissue, and with isolated nuclei has been studied. The hormone binds to an insoluble nuclear fraction. This fraction contains membranes and evidence is presented to show that estradiol is bound to the nuclear membrane. Incubation of isolated nuclei and microsome fractions with estradiol-17β shows that the hormone binds essentially instantaneously to microsomes and nuclei. Such binding is non-saturable up to estradiol-17β concentrations as great as 2.5 x 10-6 moles per mg of membrane protein and it is likely that this interaction is not biologically significant. A second form of binding is observed in nuclei which is of higher affinity and saturable, with 507 ± 47 sites per nucleus. This class of binding sites is found to be blocked in cattle that are maintained in artificially induced estrus by feeding with diethylstilbestrol.

The high affinity binding site is present only in the mature endometrium and is absent in nuclei from the mature myometrium (the muscular tissue surrounding the endometrium in the uterus) and the immature uterus. Potent estrogenic agents compete effectively with estradiol-17β for binding to this site, whereas weak estrogenic steroids (such as progesterone and testosterone) are inefficient competitors. The sensitivity of the high affinity site to pH and hydrolytic enzymes has been studied and compared with the effect of such agents on the low affinity, nonspecific, membrane site. 

Estradiol-17β causes cell proliferation in endometrial tissue approximately 48 hours after blood levels of the steroid rise 
during the estrous cycle (1). Prior to cell division there is an initial increase in ribosomal RNA synthesis (2) and 24 hours 
later an increase in DNA synthesis (3). It has been proposed that the hormone itself mediates at least.
https://www.sciencedirect.com/science/article/pii/S0021925819429256q

isolated endometrial nuclei have been presented. If the nuclei were isolated from tissue which had been exposed to diethylstilbestrol or to estradiol-17β, we observe a linear relationship between hormone input into the binding reaction and the amount bound to the nuclei.