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Welcome.

Continuing to think about this concept of lactogenesis, initiation of lactation,

beginning of lactation.

Again, it's a two stage process.

Secretory differentiation, secretory activation.

This video, we're going to focus primarily on secretory differentiation, or

things that are happening pre-partum, versus post-partum.

So pre-partum versus,

actually in that lactating tissue, we're going to focus on that initially.

Just to remind you, first of all,

mammary epithelial cells during this secretory differentiation stage,

differentiated into lactocytes, the cell that are actually going to make the milk.

With the capacity to make milk components, but

they don't necessarily, they just can't quite make a lot of them.

They make a little bit.

Coincides with limited synthesis and

secretion of milk components even before parturition.

And usually it's occurring in late pregnancy.

So let's take a look at some slides here, some images that represent,

really, the prior to lactogenesis and then actually in lactation.

So, think of lactogenesis kind of occurring in between these two time

periods.

Prepartum of lactating and prepartum mammory epithelial cell.

Over here, big nucleus, not a lot of other secretory activity, more activity

down here, secretory vesicles, no fat droplets and so on and so forth.

Let's go to the next slide.

And we can kind of characterize these cells prepartum.

We have an irregular nucleus, and so the nucleus here is, it's just not rounded.

This one down here you see is nice and rounded.

Minimal RER, rough endoplasmic reticulum,

that's where the proteins are going to be made, develop proteins.

Made up of Golgi apparatus, it's where the proteins such as casein and

others are processed.

Casein micelles are made, lactose is being made.

Not very many micovilli up here on the apical surface.

Not very many mitochondria.

Again they're kind of the energy factory of the cells.

Relatively few lipid droplets, and no secretory vesicles.

It's just kind of a fairly quiescent cell in that respect.

Go to the next slide.

Once we do get into lactation, though,

we start seeing the cell to look very very different.

So, again, a nice rounded nucleus here, compared to the one up here.

Hypertrophy of the RER and the Golgi apparatus.

Obviously a lot of metabolic activity going on.

Large secretory vesicles, so they're containing the milk product,

especially the skim milk products.

You'll find casein micelles, and perhaps just barely see some little black

dots there as an electron dense casein micelles.

Many lipid droplets, microvilli, many mitochondria.

Again, this is a very active cell so it's using up a lot of energy.

Polarized cell organelles.

What that means is that the nucleus is kind of down towards the basal side, and

you find most of the secretory vesicles and the fat droplets on the apical half

of the cell whereas this one's kind of sitting more or less right in the middle.

And then secretion of components into the lumen.

And this picture doesn't show that very much.

But again, these components are going to be secreted out in the lumen.

You're not going to find a lot of that up here in the prepartum cell.

Go to the next slide.

So just to give you again,

a reminder of some of these different organelles that we've referred to.

RER, rough endoplasmic reticulum, again these different layers here,

the little black dots are the ribosomes.

Proteins are synthesized and then end up in the lumen of the RER,

transferred over to the Golgi apparatus.

There's an example of Golgi apparatus here.

Proteins are processed.

Lactose is being produced.

Casein micelles are being put together.

And, then again, off of those will bleed off these

secretory vesicles full of lactose and milk proteins and so on and water.

Some other examples up here.

And then there's a nice fat droplet just about to be released out in to the lumen.

Go to the next slide.

This couple slides is slightly different in the sense that this is a prepartum,

just in a cow,

all these images I'm showing you in this video are from the cow.

This is a just a very few days prepartum.

So this will be kind of that phase one of that secretory differentiation phase.

And the reason we can say that is because the white area,

white drop things in here are the fat globules.

If you look very carefully, some of these cells actually have fat globules in them,

so they are starting to make milk components, just not huge amounts.

But the alveoli are smaller, they haven't flattened down yet, that is,

it hasn't kind of filled out with a lot of milk components and flattened down.

And the lactating one on the other hand, again a single layer of epithelial cells.

Lots of fat droplets, these white things are fat droplets.

Most of the blue here would be protein components

that's stained with a particular stain that was used.

And again, if we could look very carefully there,

we would be able to see that there's a lot of fat droplets and secretory vesicles.

In fact, go to the next slide, and

this is just a higher magnification of a similar kind of thing.

Again, this is just a few days prepartum.

Some fat droplets here,

obviously you have fat globules out in the lumen have been secreted.

Cells are a little bit broader, they haven't flattened down yet.

On the other hand, when we get to the actual lactating tissues, so this would be

more like what you find in the secretory activation stage, copious milk secretion.

Lots and lots and lots of secretory vesicles, fat droplets.

Here's a great big fat droplet of that ready to be secreted.

This is a lumen of one alveolus.

This is a lumen of another alveolus down here.

Again the nuclei are pretty much sunk down to the basal part of the cell

because the top part of the cell is full of all these other components.

So again very, very different looking cell activity.

Most of this is again because of a difference in cell activity making

the milk components.

Go to the next slide.

In addition to the cytological features,

there are a lot of enzymatic changes that are occurring.

Enzymatic pathways that are being increased and

enhanced during this lactogenesis process.

Glycolysis, Krebs cycle, certainly lactose synthesis, and

we'll get back to that in another video here in a bit.

Fatty acid synthesis, protein synthesis, just all those kinds of things,

all those processes that are going on in the cell that result in synthesis of milk

components and secretion of those milk components out into the lumen.

Go to the next slide.

[COUGH] So we kind of think a little bit about secretory differentiation, but

now, again, we're going to start shifting into this secretory activation.

Just to remind you again, copious milk secretion is occurring during here,

major changes in many of the milk components.

Timing is variable amongst species, and

we'll explore that here in a bit in another video.

And we start to talk about regulation of this.

And progesterone, as we'll find out later on, is a major inhibitor of lactogenesis.

So until progesterone levels fall around the time of parturition,

even though all these other things are happening,

you really can't then move into the later stage of lactogenesis.

And to review, very quickly.

Again, Secretory Differentiation, first stage of lactogenesis involves

dramatic changes in mammary cell structure and function, as we saw in this video.

An increase in cellular organelles responsible for synthesis of milk

components, so the RER, Golgi, hypertrophy of those very significantly.

Increases enzyme and cellular pathways that are responsible for

synthesis of milk components.

So lots of things happening even at this first stage of lactogenesis.

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Secretory Differentiation

Lactation Biology

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