Welcome. At this point in our various videos, we've talked about a very close relationship between what's happening in the mammary gland and mammary growth lactogenesis and getting two galactopoiesis eventually here. Maintenance of lactation. And the close association with what's happening in the mammary gland with the fact that the animal is pregnant. So again during pregnancy in the female the fetus is developing but the mammary gland is also developing around the time of parturition. Around the time when lactogenesis occurring that induction, excuse me, initiation of lactation and then maintenance of lactation once you get the go in order for the animal to continue l actating, what we're going to find is that you have to remove the milk or mammary secretions on a regular basis. Again, so far, our typical way of thinking about this, our typical thought process is these things are associated with the fact that the female is pregnant. But can you have these things happening in the absence of pregnancy? Let's go to the next slide. So that really is represented here. We've taken pregnancy out of the picture. Can the mammary gland grow in the absence of pregnancy? The answer will be yes. Can the gland undergo lactogenesis in the absence of pregnancy? And the answer will be yes. And can that lactation be maintained in the absence of that and while having giving birth, and the answer is yes. We're going to explore that over the next few videos. But before we do that, I want to go and review very briefly kind of the key regulators of what's going on in the mammary gland. So physiological process, mammary gland growth or mammogenesis primary regulators or hormones, estrogen, progesterone. There's certainly other hormones involved, for example prolactin is involved in this as well. I've underlined estrogen because we're going to keep coming back to that one. That one is really a key in terms of what's driving mammary gland growth especially during pregnancy but then in these other situations and the absence of pregnancy. Just a reminder of what those hormone concentrations kind of look like, this is again in a cow during pregnancy, so 280 day pregnancy, relative concentration, again the idea that progesterone is very very high throughout pregnancy until the very very end and drops off. And estrogen is increasing and is extremely high here in the latter half of pregnancy. Again, it's this combination of high estrogen, high progesterone that's really driving that exponential growth. But recall, the mammary gland's going to kind of grow like this, especially during this last part of pregnancy. So, estrogen is a key driver of that process. Go to the next slide. Lactogenesis, let's get a complex of hormones. Prolactin, glucocorticoids. Again, there are others involved. I have underlined prolactin because again we're going to keep coming back to that because that's a really key hormone in terms of driving this tissue through lactogenesis. State one and stage two lactogenesis. Again a reminder, so the yellow line is progesterone. And progesterone is decreasing at this end of pregnancy. Again, this is a cow, roughly from ten days pre-partum to the time of calving. This the dotted line here represents calving. Progesterone is dropping, remember progesterone is inhibitory to lactogenesis. So until it drops, our lycogens really can't occur very well. At least, certainly shifting into the second stage of lactogenisis. The blue line represents prolactin a very very high peak of prolactin. In most species, whether it's just prior to or right at the time of parturition. And then again the red line is a group of corticoid. And you get this spike, peak of glucocorticoid in the animal. And again, these things form that lactagenic complex that once progesterone drops allows that mammary tissue to shift into the stages of lactagenesis. Galactopoiesis, maintenance of lactations, once you get it going you have to keep it going. And again milk removal, removing the mammary secretions on a regular basis is critical to doing that. Otherwise it shuts itself down. And then galactopoietic hormones are also clearly involved. Prolactin again I've underlined that because prolactin is showing up in several places and we could have even put prolactin up here in mammary growth. Growth hormone, a number of other hormones. Again, we're going to focus on prolactin. Let's go to the next slide and every time the animal is nursed or the cow is milked, we get this spike of Oxytocin for milk ejection but for our purposes right now what we're really talking about is the spike of prolactin, and again, it only lasts for half and hour, forty-five minutes. Something like that. But, you get the spike of prolactin. Again, if they were nursed again you get another spike of prolactin. So that milk removal process as well as stimulating the mammary gland. Is causing a temporary or a transient spike in prolactin concentration in the animal. So with this kind of reminder of what we have talked about in other videos with regard to hormonal regulation of mammary growth, lactogenesis. Haven't gotten to yet, but we will get there. Again, we would need to come back then and ask the question or think about lactation in the absence of pregnancy. And I indeed provide some terminology here for you, some vocabulary. Non-puerperal lactation is lactation without giving birth. Puerperal, this word here means something to do with, or associated with, giving birth, or parturition around that time frame. So non-puerperal lactation would be lactation without giving birth. And so that's kind of a broad-based term, that we can use for variety of the kinds of things that we going to think about in this video, as well as others. Also need to remind you, galactorrhea, or lactorrhea. We've talked about that a little bit before. Abnormal or spontaneous flow of milk from the breast, which is not associated with childbirth of nursing, this is very, very often associated with our species with especially with women, can using the word breast rather mammary gland reported in 5-30% of woman. So, it’s really not done in common We want to then start looking at specific instances of where of non-peurperal lactation and some of those will feed back into galactorrhea, as we think about that. And here, what we want to talk about is induction of lactation. Induction of lactation, this is a term, process of inducing lactation in a mother that has never lactated or not lactated for some period of time. And that can be, this is kind of the definition used for women. The other way of thinking about this is something called relactation. Relactation is a situation where a woman would have started lactating for some reasons stopped and then after say a few weeks or a few couple of months once they start lactating again. That's a little bit different that we are talking about here because this is a case where they have never either lactated before or perhaps lactating hasn't lactated for or some extended period of time. We're talking about now is hormonal induction of lactation in non-pregnant cattle. So the ideas this works best in multiparous, dry cows. So the cow is been through one lactation, it's not more. They are dry meaning they're not lactating at that point. And they're also open or not pregnant. The typical way of doing is to administer, inject high levels off estrogen and progesterone for about seven days. This is again mimicking that very high estrogen and progesterone that you'd see during pregnancy. It really starts that mammary gland to regrow. Recall also that the high level of estrogen is going to induce or cause an increase in prolactin secretion, and prolactin being both for Mammary gland growth but also then shifting that gland into lactagenesis. Sometimes people use a source of glucocorticoid, one way or the another, either directly or sometimes they administer the ACTH or adrenocorticotropic hormone, which would come from the pituitary, go to the adrenal gland and cause secretion of glucocorticoids. So sometimes that's used, sometimes not. Sometimes people administer some sort of a drug to increase prolactin secretion even further. And then again recall that both prolactin and glucocorticoid or part of that lactogenic complex. And that's again shifting that tissue Into lactogenesis but then at about 18-21 days you just start removing whatever mammary secretion is there. Because removal of that mammary secretion is important for keeping that lactation function going. As well as to keep the mammary gland growing as well as to keep everything moving along. With regards to what the mammary gland looks like at that point, a lot of the times people will just start removing the milk. Response is quite variable, but certainly is relatively succesful in these kinds of animals. Some have even then, once you start removing the milk, some have actually start administering bovine growth hormone or also known as BSG. To further enhance the lactation response because this hormone in this species is a galactagogue, it will further enhance milk production. So this is for a cow, let's go to the next slide. So we've covered all the bases haven't we. We've talked about the hormones that control mammary gland growth Lactogenesis and then keeping the thing going, keeping the mammary gland going once we start removing the milk. In other species, again, you find a similar kind of protocol in women who want to undergo induction of lactation. Typically, they use birth control pills of one sort of another to mimic this. And then, sometimes use a variety of kinds of drugs to enhance prolactin secretion. There's several different kind of drugs that will cause prolactin secretion to go up. And then, again, start expressing the milk or using pumps to remove the milk and to make sure the gland gets going o it can also occur in women. This kind of general protocol would probably be pretty effective in most mammalian species. So let's go to the next slide. So just kind of a very quick review here because this sets up some of the next videos that we have. Just to remind you again mammary gland growth Estrogen progesterone. I put it in kind of pink or purple here. We're going to focus a lot on estrogen and some of these other ways of causing mammary gland development and then eventually lactation in the absence of pregnancy. Galactopoiesis again and again I've underlined and put in pink here prolactin. "Cause again, that's a really key one. These are, these are two that are really critical for thinking about this lactation and, and all these different ways of getting the mammary gland to function in the absence of pregnancy. Again, galactopoiesis somewhere alone the line, that secretion needs to be removed if we're really going to shift this into true lactation" and again, prolactin's certainly involved and contributes to this galactopoietic function in the gland as well.