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S2: Neuroscience : 2:00-3:00
Scribe: Andrew Treece
Monday, March 9, 2009
Proof: Sheena Harper
Dr. Keyser
Neuroendocrine System
Page 1 of 4
ANS=autonomic nervous system
GH= growth hormone
LH=luteinizing hormone
TSH=thyroid stimulating hormone
TRH=thyrotropin releasing hormone
ACTH=adrenocorticotropic hormone
FSH=follicle-stimulating hormone
GnRH=gonodotropin releasing hormone
CRH=corticotrophin releasing hormone
OT=oxytocin
GRHR= growth hormone releasing hormone
I. The Neuroendocrine System [S1]:
II. Overview [S2]
a. We are going to talk briefly about the anatomy of the hypothalamus and pituitary.
b. We’ll talk about the function of the hypothalamus.
c. We’ll talk about the neuroendocrine control of pituitary hormones.
III. The Hypothalamus [S3]
a. This is an MRI image of a person and the arrow is pointing to the hypothalamus.
b. The hypothalamus is intimately involved with the ANS.
c. It controls the four F2:
Fighting, fleeing, feeding, and reproduction.
IV. [S4]
a. So there is a central autonomic network that integrates visceral sensory information and coordinates autonomic
output, and the hypothalamus is a key component of this system.
b. They hypothalamus forms the floor and ventral walls of the third ventricle. It is continuous through the
infundibular sac with the posterior pituitary.
c. The hypothalamus controls blood flow, particularly cardiac output, vasomotor tone, and blood osmolality and
renal clearance.
d. It regulates energy metabolism by monitoring blood glucose, regulates feeding, digestive functions, metabolic
rate, and body temperature.
e. It regulates reproductive activity, gender identity, sexual orientation, mating behavior, menstrual cycles,
pregnancy, and lactation.
f. It coordinates responses to threatening conditions, maintains a balance between sympathetic and
parasympathetic activity.
g. So the way the hypothalamus does all this is that it compares through a variety of sensory structures what is
going on in the body at that moment to certain set points, for example to body temperature or for blood
osmolality or for the degree of hunger vs. satiety. So it compares all of that to a set point then activates
responses appropriate to bring the system back to that set point.
h. In the case of a fever, the temperature set point is screwed up so the body temperature is set at a higher level.
V. Subdivisions of the Hypothalamus [S5]
a. The hypothalamus is incredibly complicated and involves about 50 nuclei, all of which do different things.
b. Anterior hypothalamic area is involved with blood pressure control, thirst, and temperature regulation.
c. Posterior hypothalamic area is involved with blood pressure and temperature regulation as well.
d. Paraventricular nucleus for water balance OT and vasopressin release.
e. Supraoptic nucleus for osmoregulation, water balance, vasopressin release.
f. Lateral hypothalamic area for feeding and energy balance.
g. Ventromedial nucleus for satiety and energy balance.
h. Suprachiasmatic nucleus is for circadian rhythms.
i. Preoptic area for sexual differentiation and behavior and reproductive function.
j. Dorsal hypothalamic area contains dopaminergic neurons
k. Arcuate nucleus with dopaminergic neurons.
l. Median eminence which is a final common pathway for outputs to the pituitary.
VI. The hypothalamus is a cluster of about 50 interconnected nuclei [S6]
a. So here is our human brain (sagittal section) with the hypothalamus labeled. Pointed out are some of the 50
nuclei just mentioned.
b. The supraoptic nucleus is just above the optic chiasm and seems to be the master clock for controlling circadian
rhythms.
c. He pointed out the optic chiasm, anterior pituitary, posterior pituitary, the dorsal medial nucleus, lateral and
medial preoptic nuclei, but did not say anything about them.
VII. Hypothalamus integrates autonomic activity and the endocrine system[S7]
a. This is a coronal view.
b. This integrates autonomic activity and the endocrine system. It turns out that the neurons along the wall of the
third ventricle manufacture peptides known as releasing or inhibiting factors. These control the release of
hormones by the anterior pituitary.
S2: Neuroscience : 2:00-3:00
Scribe: Andrew Treece
Monday, March 9, 2009
Proof: Sheena Harper
Dr. Keyser
Neuroendocrine System
Page 2 of 4
c. The axons from these cells project to the median eminence which is just above the pituitary at the
hypothalamus-pituitary junction.
VIII. Brain section diagrams [S8]
a. So there area paraventricular cells and cells in the supraoptic nuclei that contain neurosecretory neurons whose
axons extend into the posterior pituitary. Those other ones we talked about before produce releasing or
inhibiting factors that can control or release hormones from the anterior pituitary.
b. These here have axons that go down to the posterior pituitary, and the neurons can secrete OT and vasopressin
into the blood stream.
IX. Hypothalamic releasing factors summary[S9]
a. I made this table just to show you what the factor is, what the target is, what the hormone released by the target
is, and the target tissue.
ANTERIOR PITUITARY
b. In the hypothalamus, GRHR is released, it targets somatotroph cells in the anterior pituitary, causing them to
release GH, which targets all types of somatic tissues.
c. TRH produced in the hypothalamus targets the thyrotroph cells in the anterior pituitary, they release TSH that
targets thyroid cells.
d. CRH target corticotrophs in the anterior pituitary, these in turn release ACTH, which targets the adrenal cortex
causing it to release corticosteroids, glucocorticoids to be specific.
e. GnRH targets gonadotrophs in the anterior pituitary, they release FSH and LH and these target the gonads,
and they affect the Leydig cells in the testes required for spermatogenesis and testosterone production, and
they target the follicle cells in the ovary for estrogen and progestin production.
f. Finally, there are cells in the anterior pituitary called lactotrophs and these produce prolactin which targets
mammary glands to increase milk production, and notice that there is no anterior pituitary releasing factor made
in the hypothalamus to target the lactotrophs in the anterior pituitary and we will talk about that later.
POSTERIOR PITUITARY
g. The posterior pituitary is different:
h. We have vasopressin and OT generated by cells in the hypothalamus, they are released into the bloodstream of
the posterior pituitary and they affect collecting ducts increasing permeability to water for vasopressin and
uterine and breast tissue for OT.
X. Feedback loop and hierarchical control[S10]
a. There are two basic feeback models.
b. Figure A is the simple feeback loop. That is where a sensor, for example a Beta cell in the pancreatic islet,
detects some regulated variable, for example plasma glucose. It responds by modulating secretion of a
hormone, like insulin. So the sensor modulates hormone release, and this hormone in turn acts on a target,
Target 1, for example liver or muscle, to modulate the production of another hormone or metabolite, that is in
this case glucose that can be made in the liver. This in turn can affect a second target and so on. In addition
this feeds back to the original sensor cell, the pancreatic beta cell. So this is a simple feeback loop where the
other metabolite, like the glucose made in the liver, feeds back to the sensor.
c. Figure B is the hierarchical control and is a little more complicated. In this case under the influence of the
cerebral cortex, cells in the hypothalamus release CRH, which in turns stimulates ACTH release from cells in
the anterior pituitary. These release ACTH which feeds back and in turn activates cells in the adrenal cortex to
make glucocorticoids and these target target tissue. In the mean time, the cortisol can feed back on the ACTH
producing cells in the pituitary and can also feed back on the hypothalamus.
d. So this is hierarchy where there are many levels of organization, and feeback affects these multiple levels or
organization.
XI. The hypothalamus pituitary axis diagram[S11]
a. ***NOTE CORRECTION***: the words “posterior pituitary” in the 18th line should be omitted.
b. This is a cartoon of the hypothalamus. Here is the anterior pituitary and the posterior pituitary.
c. You can see the infundibular stalk, the median eminence, and many of those nuclei discussed in the
hypothalamus.
d. So the pituitary is actually two glands, the anterior pituitary and posterior pituitary, and they are really, really,
really different. In both cases the hypothalamus controls the secretion of hormones but the mechanisms are
different.
e. Anterior pituitary first: So small bodied neurons in several nuclei that surround the 3 rd ventricle and that
includes the arcuate, paraventricular, and ventral medial nuclei, medial preoptic nuclei, secrete releasing
inhibitory factors into a rich funnel shaped plexus of capillaries that penetrates the median eminence, and
surrounds the beginning of the infundibular stalk. The capillaries coalesce into these long portal veins that carry
the factors down into the anterior pituitary. Other cells in the hypothalamus secrete into capillaries that make up
S2: Neuroscience : 2:00-3:00
Scribe: Andrew Treece
Monday, March 9, 2009
Proof: Sheena Harper
Dr. Keyser
Neuroendocrine System
Page 3 of 4
the short portal veins and deliver releasing factors to the troph cells again in the anterior pituitary, and these
cells are going to release GH, TSH, ACTH, LH, and FSH.
XII. Circumventricular organs[S12]
a. You all have heard about the blood brain barrier before, so there is a specialization of the nervous system called
circumventricular organs and these you can think of as windows on the brain because they are places where the
blood brain barrier doesn’t exist.
b. In regions of the 3rd and 4th ventricles, these regions are highly vascularized and the capillaries are fenestrated
which means they let high molecular weight substances pass from the blood to the brain.
c. There are specialized cells, tanycytes, that connect the ventricle of the brain to the adjacent neural tissue, and
there are receptors for hormones that control fluid volume, electrolytes, and cardiac function.
d. The neurons in these regions project to other regions involved in Neuroendocrine and cardiac control.
e. So the circumventricular organs where the blood brain barrier is missing include among others the posterior
pituitary, and the median eminence.
f. This shows a diagram of what the blood brain barrier actually is, a combination of vascular endothelial cells and
they line the vessel and where they stop there are tight junctions that prevent fluid and molecules from moving
between them, and they are surrounded by divider cell types like astrocyte end feet so that anything that moves
between the blood and brain in most of the brain has to pass between these cells. So the things that can pass
through are tightly regulated.
g. So again, the circumventricular organs which include posterior pituitary and the median eminence are where the
blood brain barrier is lacking.
XIII. Posterior pituitary [S13]
a. In this case, large neurons in the paraventricular and supraoptic nucleus synthesize vasopressin and OT, and
these hormones travel down the hypothalamic axons to the posterior pituitary where the nerve terminals actually
release the hormones.
b. Since the posterior pituitary is one of those circumventricular organs where there is no blood brain barrier, the
vasopressin and OT that is released from these hypothalamic cells can get into the general circulation.
c. So on the one hand in the anterior pituitary we have these releasing or inhibiting factors which are brought down
in the portal system in the blood vessels from hypothalamic neurons and control the release of these cells from
all those neurons.
d. In this case with the posterior pituitary we have OT and vasopressin being released from the hypothalamic cells
themselves and they get into the blood stream directly.
XIV.
Hormones secreted by the pituitary [S14]
a. So here are the hormones secreted by the pituitary. READ DIRECTLY FROM CHART*****
Anterior
Pituitary
Hormone
Major target
organ(s)
Growth hormone
Liver, adipose
tissue
Thyroid-stimulating
hormone
Adrenocorticotropic
hormone
Promotes growth (indirectly),
control of protein, lipid and
carbohydrate metabolism
Stimulates secretion of thyroid
hormones
Stimulates secretion of
glucocorticoids
Luteinizing
hormone
Follicle-stimulating
hormone
Adrenal gland
(cortex)
Mammary
gland
Ovary and
testis
Ovary and
testis
Vasopressin
Kidney
Conservation of body water
Oxytocin
Ovary and
testis
Stimulates milk ejection and
uterine contractions
Prolactin
Posterior
Pituitary
Thyroid gland
Major Physiologic Effects
Milk production
Control of reproductive function
Control of reproductive function
XV. Pituitary: Master gland of endocrine system[S15]
a. So the pituitary you can think of being the “master gland” of the endocrine system.
b. The anterior pituitary is what we’re going to talk about first, and you can see that hormones coming from this
gland affect most of the major organ systems: ovary, testis, adrenal cortex, thyroid, liver, mammary gland. Then
these give rise to products that affect many other tissues in the body.
S2: Neuroscience : 2:00-3:00
Scribe: Andrew Treece
Monday, March 9, 2009
Proof: Sheena Harper
Dr. Keyser
Neuroendocrine System
Page 4 of 4
c. So we are going to take these one at a time.
XVI.
The GnRH-FSH/LH Reproductive Hormone Axis[S16]
a. Gonodotropin releasing hormone, follicle stimulating hormone, and luteinizing hormone.
b. We are going to talk about these all at once.
c. We have simplified cross sections of the hypothalamic structures we’re talking about.
d. So in this case neurons in the arcuate nucleus produce GRH and release it near the portal vessels near the
median eminence. Blood vessels convey it to the anterior pituitary, where it affects gonadotrops (or
gonadotrophs); the gonadotrops are activated causing the release of LH and FSH. So GRH is released in a
pulsatile manner from these cells in the arcuate and preoptic nuclei and there is a surge of about one per hour.
There is a corresponding pulsatile release of LH and FSH. So these can cause ovarian cells to produce
estrogen and progestin. LH can cause the testes to produce testosterone, and FSH causes the Sertoli cells of
the testes to synthesize a number of products needed by the Leydig cells and developing spermatogonia.
e. So LH and FSH affect both the male and female reproductive tracts.
XVII. The CRH-ACTH-Corticosteroids Axis [S17]
a. So in this case, CRH comes from cells in the paraventricular nucleus. They release it in the median eminence
into the portal system, and these affect corticotrophs in the anterior pituitary, and these cells release ACTH.
That causes cells in the adrenal cortex to release glucocorticoids. Glucocorticoids in turn affect the liver for
glucose synthesis and for muscle, for example for protein breakdown to release amino acids and adipose tissue
for the mobilization of fat.
XVIII. The TRH/Dopamine-Prolactin AxisS18]
a. So the arcuate nucleus, and perhaps the median eminence although that’s not clear, of the hypothalamus
synthesize TRH. This stimulates the release of thyrotropin from thyrotrophs of the anterior pituitary. These
release TSH which in turn stimulates the cells of the thyroid to produce thyroid hormones that act on many,
many tissues.
XIX.
Regulation of Prolactin [S19]
a. The regulation of prolactin is very different.
b. So in all the other cases we talked about there were releasing hormones that were generated in the
hypothalamus.
c. In this case, prolactin is actually produced in the pituitary independently of the hypothalamus throughout life and
has effects in both males and females. However, its only major function is only in females and then only at a
specific time.
d. Now left to its own devices the pituitary would generate high levels of prolactin, but it turns out the release is
tonicly inhibited by dopamine from cells in the arcuate nucleus. So it can keep the level of prolactin synthesis
and release at a low level in both males and females except during certain times in a female’s life.
e. So during breast stimulation in suckling, neuroafferents inhibit dopamine release, which relieves the lactotrophs
of their tonic inhibition so they can generate more prolactin.
XX. Several factors act as prolactin releasing factors [S20]
a. Several factors act to modulate prolactin release.
b. For example, TRH release from the hypothalamus is also stimulated by suckling in lactating females, and TRH
causes increased milk production.
c. Estradiol increases the sensitivity of lactotrophs to TRH and decreases the sensitivity to dopamine, so that
works in two different ways.
XXI.
Two final points [S21]
a. There neurons in the spinal cord that get sensory information from the periphery, for example when suckling,
and the sensory input inhibits neurons in the arcuate and preoptic areas which causes a reduction in the release
of GRH. This in turn inhibits the ovarian cycle so this is natures birth control circuit.
b. In addition, the sensory input from cells in the spinal cord causes increased synthesis and release of OT into the
posterior pituitary and this promotes uterine contractions and assists in milk ejection.
c. So the Neuroendocrine axis is incredibly important and together with the autonomic system, these systems
control almost every aspect of physiology ranging from pupillary dilation or constriction to regulating the
reproductive cycle.
So the things he wants us to know from this are:
The important hormones prolactin, ACTH, gonadotropin, FSH, and LH, and that’s it, just those guys.
****I am not sure what he is talking about when he says just know these, whether he is talking about just for that
last part or what.
(end time 27:54)