Welcome, we've been exploring this idea of non-puerperal lactation- lactation without giving birth, lactation in absence of pregnancy. And we've also been talking a lot about the idea of galactorrhea, especially in humans, but certainly in other species as well. Abnormal or spontaneous flow of milk from the breast, which is not associated with childbirth or nursing. And again, in our own species, it's really not that uncommon in women. And so, in this video we're going to focus on prolactin as being one of the parts of how we think about these kinds of things. Let's go to the next slide. So just as a reminder. Physiological processes, mammary growth, lactogenesis, galactopoiesis or maintenance of lactation and again, estrogen, progesterone are involved in mammary growth. I've actually added up here prolactin because. Just to remind us that prolactin's also involved in the process of mammary development, mammary gland growth. So, certainly prolactin is heavily involved in lactogenesis, and then even once lactation gets going prolactin is a key component of that. So, again, this video's going to be about prolactin, and how we might think about prolactin, in terms of this non-pure prolactation idea, or galactoria. Let's go to the next slide. So [COUGH] to start our thought process on this, we need to think about where's prolactin going to come from? So, prolactin-like activity. Those come from the placenta. Most of that is placental lactogen activity, that's coming actually from the placenta. Here we're talking about an animal that's not pregnant. So, we can kind of discount that one. We're really not going to talk much about that one. The other source, the primary source of prolactin, is the anterior pituitary. Let's go to the next slide. And a lot of times what happens is, this is defined in the context of elevated or persistently elevated prolactin concentrations in the blood. And that's referred to as hyperprolactinemia, persistently or excessively elevated blood prolactin. How might that be happening? Let's go to the next slide. So, some of the causes of hyperprolactinemia are variety of drugs. So ,dopamine antagonists and there's several of them listed here. Dopamine antagonists recall the prolactin the normal regulation of prolactive from the pituitary hypothalamus releases dopamine and dopamine inhibits. Or suppresses prolactin suppression from the pituitary, so an antagonist from dopamine would allow prolactin to be, getting in the way of the dopamine doing it's job. It releases that inhibition of prolactin secretion, and prolactin can then be secreted persistently or excessively. So again, some of these dopamine antagonists. Again, drugs that are many times used in human medicine and other situations. Antidepressants, some of those. Again, a lot of these things have effects, other effects on the brain. Anti-hypertensive drugs, reserpine is one of those that comes from plants Rauvolfia serpentina, Indian snakeroot plant, been used for a long time. Has unfortunately a lot of other side effects, and so people don't necessarily use it as much anymore, but it is something that will cause prolactin concentration to go up rather than down. Estrogens, we've talked about those before. Opiates, a whole bunch of other kinds of drugs that can impact prolactin secretion from the pituitary. Hypothalamic disorders again, where the dopamine suppression collected is not working properly. Pituitary disorders prolactinomas and we're going to get back to those here in just a moment or two. Primary hypothyroidism, recall that the hypothalamus, pituitary, thyroid access. Thyroid releasing hormone goes from the hypothalamus, is released, causes release of thyroid stimulating hormone from the pituitary, anterior pituitary, same place that prolactin is coming from. That goes to the thyroid gland causing release of the thyroid hormones. So, part of that access is the negative feedback, the thyroid hormones going back to the hypothalamus and suppressing more TRH. So that's how we get hormones balanced and maintain their consecration. If for some reason the thyroid gland is not responding to the TSH there's nothing there's no negative feedback or limited negative feedback, so that the system just think that needs to release more and moe, more TRH or more the thyroid releasing thyroid stimulating hormone. But the thing that we need to point in there that comes back to the hyperprolactinemai is TRH, thryoid releasing hormone, thryotropin releasing hormone excuse me also releases prolactin. So, the more TRH being released in the hypothalamus the more proclatin that is secreted as well as fire stimulating hormone, so that's where this primary hypothyroidism comes into play, in the hyperprolactinemia. Neurogenic, this idea of stimulation of nerves, and usually in the chest region or the breast or nipple region. So chest lesions, breast or nipple stimulation. We'll get back to that, just a little bit more information on that as well. And then, stress and a variety of other things can feed back into this hyperprolactinemia. Let's go to the next slide. And just to remind you, because we've talked about this in other videos, that these things are all by definition galactogogues. They're going to have an impact on the mammary gland and the mammary gland function. And it's usually through this hyperprolactinemia. Next slide. So, let's focus now on the prolactinomas [COUGH] excuse me. And again, in association with hyperprolactinemia. These are pituitary tumors they care for 40% or all pituitary tumors. So, they are very very prevalent in terms of the proportion of pituitary tumors that are found. Again, a lot of these data comes from our species, humans. Galactorrhrea is observed in a large proportion of women that have hyperprolactinemia that is associated with the pituitary tumors or prolactinoma. So again, this close relationship between prolactinomas, hyperprolactinemia and galactorrhea, all of these things very often come together. It's observed in adult females and males, although less common in children and adolescents. They define the prolactinomas basically by size or diameter. So, what they call micro-prolactinomas are less than 10 mm in diameter. Macro-prolactinomas are bigger than 10 mm diameter. Other manifestations are the, primary clinical manifestations including infertility, in adults, sexual dysfunction and then also very often again Galactorrhea. How do you treat this? Again, we have kind of the prolactin is just being secreted because there's no inhibition of that, well then we use a dopamine agonist to then suppress that prolactin secretion. So again, several kinds of drugs that, some of these we've talked about before in other videos. So again, these are all dopamine agonists. Next slide. [COUGH] Now what I want to do is to talk about more about some other elements of this again remembering the prolactic comes into play at all of this different points, to the next line. So, we call that every time the animal is nursed. You have milk removal, stimulation of the breast, stimulation of mammary gland. You get this not only release of oxytocin from milk injection but also this release of prolactin. So again, our example here of a cow. Just kind of a idealize prolactin spike. So, there is some surge or some transient surge of prolactin every time the mammary gland is stimulated. To the next slide. So this feeds back into this idea of the neurogenic causes of hyperprolactinemia, and then how that fits back into galactorrhea. So chest lesions, so chest surgery, down here, chest surgery, nipple piercing. Again, that constant stimulation. Causing the same nerves that are going to cause milk ejection for example also going to result in prolactin release and again this is going on repeatedly it's not just once in a while. So persistent stimulation of those nerves can cause elevated prolactin secretion and then potentially leading back here to galactorrhea. What is called sucking-induced lactation? So, again, this is repeated, persistent stimulation of the breasts, the nipples, the mammary gland, can cause hyperprolactinemia, and, again, eventually galactorrhea. Just as an aside here, in cattle, we know that every newborn mammal has a very strong suckling reflex. A sucking drive. And eventually they outgrow that. But what we can find even in cows, 1.5, 2% of the cows, adult cows have been observed to suckle other cows so again we call this inter suckling. So, it's certainly a possibility and as well think about hyperprolactinemia that this is being caused because of generically we call this a neurogenic causes of hyperprolactinemia. Again, potentially leading back to our galactorrhea. To the next slide [COUGH]. So talk about hypoprolactinemia. Elevated prolactin. What about suppressed prolactin? Obviously, that would go against the idea of lactogenisis and lactation and so on. This is a deficiency of blood prolactin and I wanted to introduce this idea. We've actually talked about this incorrectly in some other ways. You've seen some of these things before ergots. The ergot alkaloids, the ergot fungi, group of fungi from the genus Claviceps. And this particular one is the best known of the ergot fungi. It's also been referred to as rye ergot fungus. Certainly, evidence even dating back to the middle ages of this having an impact on mammals, animals, and so on. It causes ergotism in mammals, including a range of symptoms, and it has a range of symptoms, these compounds that are in the fungi. As you see here, the momenta sclerosa, where it's actually contained. And again a range of symptoms, the one's we're concerned about with regard to the mammary gland are basal constriction. So, constriction especially in extremities. And then, decrease in prolactin secretion and that feeds back into what we're talking about in terms of, again, lactation. That's not being raised prolactin, that's being suppressed. The ergot sclerotia, which are basically these kind of hardened mycelia, packaged together there. And they also contain the alkaloids, which are what's actually causing the vasoconstriction and inhibition of prolactin secretion. Are responsible for most of the symptoms that we see in this ergotism. Ergotamine is a drug that's been used in human medicine. It's one that kind the primary example of an erganalcaloid that has these kinds of effects. Bromocriptine, we've run into before because we've talked about this in a number of videos. This really synthetic ergoline derivative, and again it's a dopamine agonist, so it's suppressing prolactin secretion. So that's hyperprolactinemia. Let's go to the next slide. So just to kind of wrap up and review some of the things we've talked about here, again focusing primarily on prolactin. Prolactin coming in at all these different components of mammary growth, mammary function. And again, in terms of how prolactin might impact this especially both in the physiological sense but also in the sense of where the animal is not pregnant. So, we don't have the normal concentrations, the normal flocks in concentrations of prolactin that we would see in pregnant animal, for example or lactating animal. We call that hyperprolactinemia, persistently high prolactin concentrations in the blood. And a variety of kinds of things, briefly about the dopamine antagonists. We talked a little bit about the prolactinomas, and neurogenic stimulation. And certainly again, there's a variety of ways that prolactin can be enhanced. Go to the next slide. And so, again, this idea of Dopamine antagonists, excuse me, antagonists, Dopamine antagonists, again, prolactin secretion is suppressed by Dopamine. If you kind of release that, if the Dopamine antagonists get in the way of Dopamine doing its job, prolactin secretion's going to increase. Increased demands. Again, a variety of these things causing hyperprolactinemia. Hypoprolactinemia on the other hand due to deficiency of blood prolactin that we see in a set of drugs that will suppress prolactin concentration. So again, both of these things come into play. The antagonists as well as these hypoprolactinemia the agonists. The agonists are used in human medicine as well as used in some other species to control prolactin secretion. Dopamine agonists again are the ones that are causing this hypoprolactinemia. So, there's variety of ways to try to manage our order for pick control of collective secretion especially when situations where we want to do that on purpose either we have hyperprolactinemia will want to bring up for like them down or vice versa we want to increase for like a concentration for some reason
