Lecture 1 and 2 Introduction and Hypothalamus/pituitary (I & II)

Question 1

What does the hypothalamus do?

Answer 1

The body’s normal, balanced state of being is known as homeostasis. The body is always trying to achieve this balance. The main job of the hypothalamus to keep the body in this state as much as possible.

It is also in control of the hormone secretion by the anterior pituitary gland.

The hypothalamus plays a huge role in both the endocrine and nervous systems.

To do this, the hypothalamus acts as the connector between the endocrine and nervous systems. It plays a part in many essential functions of the body such as:

• Body temperature
• Thirst
• Appetite and weight control
• Emotions
• Sleep cycles
• Sex drive
• Childbirth
• Blood pressure and heart rate
• Production of digestive juices
• Balancing bodily fluids

Question 2

What does the Pituitary Gland do?

Answer 2

Secretes multiple hormones that regulate the endocrine activities of the adrenal cortex, thyorid gland and reporductive organds, and a hormone that stimulates melanin production.

Question 3

What part of the brain is diencephalon part of?

What brain structures make up the diencephalon?

Answer 3

Part of the forebrain

Made up of:

• Thalamus
• Hypothalamus
• Epithalamus

Question 4

How does the Diencephalon develop?

Answer 4

Hypothalamus develops from the hindmost part of the forebrain – the diencephalon.

Question 5

Describe the development of the pituitary gland

Answer 5

The pituitary gland is entirely ectodermal in origin but is composed of 2 functionally distinct structures that differ in embryologic development and anatomy: the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary).

The adenohypophysis develops from Rathke’s pouch, which is an upward invagination of oral ectoderm from the roof of the stomodeum; in contrast

The neurohypophysis develops from the infundibulum, which is a downward extension of neural ectoderm from the floor of the diencephalon.

Question 6

What is another name for “Anterior Pituitary”

Answer 6

adenohypophysis

Question 7

What is another name for “Posterior Pituitary”?

Answer 7

Neurohypophysis

Question 8

Reproduction is controlled by a ___________

Answer 8

Reproduction is controlled by a hierarchical arrangement of endocrine glands with the
hypothalamus as the ‘master regulator’.

Question 9

Describe the basic hormonal feedback control of the hypothalamus and antieror pituitary

Answer 9

1) Stimulus comes in
2) Hypothalamus releases Hormone 1 (GnRH) onto the Anterior Pituitary
3) Anterior pituitary releases Hormone 2 (LH, FSH) onto the Gonads
4) The Gonads release Hormone 3 (17-B-estradiol = E2) onto the Target tissue

Feed-back may be negative or positive, and alteration of one component in a feed-back loop will lead to an alteration in another component, other things being equal.
In most cases limitations on the secretions of hormones are provided by negative feedback action of the target organ hormone or secretory product on the gland supplying the trophicstimulus, and/or its hierarchial superior. Changes in hormone concentrations are of primary importance, eg circhoral (hourly) release of GnRH, circadian (24hr) release of ACTH and cortisol, monthly peak of LH in women.

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Question 10

Hormones secreted by the hypothalamus are produced by _____

Answer 10

Hormones secreted by the hypothalamus are produced by neurons aggregated into ‘nuclei’.

Question 11

Hypothalamic hormones are released from axon terminals work either _______ or ______

Answer 11

Hypothalamic hormones are released from axon terminals either directly into the general
circulation (posterior pituitary) or into a portal system of veins for direct transport to anterior
pituitary.

Question 12

Feed-back loops from target organs control release of hormones from the hypothalamus.
Feed-back is mostly ______, but is_____ during _______

Answer 12

Feed-back loops from target organs control release of hormones from the hypothalamus.
Feed-back is mostly negative, but is positive during early-mid menstrual cycle.

Question 13

Secretion of hypothalamic hormones is ______, that is they are released_______

Answer 13

Secretion of hypothalamic hormones is pulsatile, that is they are released in d_iscrete bursts_

Question 14

Where is the hypothalamus?

Answer 14

Question 15

What structures surround the hypothalamus and the pituitary gland?

Answer 15

AC: Anterior commisure

PC: Posterior Commisure

LT: Lamina terminalis

OC: Optic chiasm

MB: Mammillary bodies

IS: infundibular stalk

TC: Tuber Cinereum

MT: Mammillothalamic tract

PF: postcommissural fornix

Question 16

Name the major nuclei of the hypothalamus

Answer 16

1) Paraventricular (PVN)
2) Supra-optic (SO)
3) Parvicellular

Question 17

What are the 2 parts of the pituitary (both names for both)

Answer 17

Pituitary gland consists of 2 lobes

1) Anterior (Adenohypophysis)
2) Posterior (Neurohypophysis)

Question 18

Describe the Blood supply to the hypothalamus and the pituitary

Answer 18

1. Superior hypophyseal artery
2. Anterior hypophyseal veins
3. Inferior hypophyseal artery
4. Posterior hypophyseal veis
5. Primary plexus of hypophyseal portal system
6. Hypophyseal portein veins
7. Secondary plexus of hypophyseal portal system
8. Capillary plexus of infundibular process

Question 19

How does the hypothalamus interact with the pituitary gland?

Answer 19

1) Supraoptic nuclei and Paraventricular Nuclei

-Neurons of these structures manufacture antidiuretic hormone and oxytocin, respectively, which are released by the snypatic terminals at capillaries in the posterior lobe of the pituitary gland.

2) Hypophyseal portal system

• The capillary networks in the median emience are supplied by the Superior hypophyseal artery.
• Before leaving the hypothalamus, the capillary networks unite to form a series of larger vessels that spiral around the infundibulum to reach the anterior lobe
• Once within the anterior lobe, these vessels form a second capillary network that brnaches among the endocrine cells.

Question 20

The capillary networks in the median emience are supplied by the ____________

Answer 20

The capillary networks in the median emience are supplied by the Superior hypophyseal artery.

Question 22

Neurons from the Supraoptic nuclei and Paraventricular Nuclei release….

Answer 22

-Neurons of these structures manufacture antidiuretic hormone (Supraoptic nuclei) and oxytocin (Paraventricular Nuclei), respectively, which are released by the snypatic terminals at capillaries in the posterior lobe of the pituitary gland.

Question 23

What hormones are released from the hypothalamus and released via the hypophysial portal system?

Answer 23

1. Gonadotrophin-releasing hormone
2. Thyrotropin-releasing hormone
3. Corticotropin-releasing hormone
4. Prolactin-releasing hormone
5. Prolactin-inhibting hormone
6. Growth hormone-releasing hormone
7. Somatostatin

Question 24

What hormones are released from the pituitary? (6)

Answer 24

1. Follicile-stimulating hormone
2. Luteinizing hormone
3. Thyroid-stimulating hormone (thyrotopin)
4. Adrenocorticotropic hormone
5. Polactin
6. Growth hormone

Question 25

Which is one anterior and which one is posterior pituitary? And why?

Answer 25

In the posterior pituitary, there are axonal processes (these don't stain very well) In the anterior pituitary, there are lots of secreting cells and cell nuclei (lots of hormone synthesis)

Question 26

What are these? Where are they found?

Answer 26

Anterior pituitary Pink: **Acidophils** (50% are somatotrophs and 20% are mammotrophs) Purple: Basophils (20% Corticotrophs, 5% Thyrotrophs and 5% Gondaotrophs)

Question 27

Describe the Histology of the Anterior Pituitary

Answer 27

1. Pink: **Acidophils** (50% are somatotrophs and 20% are mammotrophs) 2. Purple: **Basophils** (20% Corticotrophs, 5% Thyrotrophs and 5% Gondaotrophs)

Question 28

What are the different types of acidophils?

Answer 28

Acidophils (50% are **somatotrophs** and 20% are **mammotrophs**)

Question 29

What are the different types of Basophils?

Answer 29

Purple: Basophils (20% **Corticotrophs**, 5% **Thyrotrophs** and 5% **Gondaotrophs**)

Question 30

What are these cells and what do they produce?

Answer 30

Question 31

Describe the Hypothalamic and Pituitary hromones and some effects on the target tissues

Answer 31

Question 32

Describe the process of release of Growth Hormone

Answer 32

* GH involves both releasing and inhibting hormones * The _arcuate nucleus_ releases the _GH-releasing hormones_ into the Anterior lobe. * Here, the Anterior Lobe releases the _Growth hormones_ * GH influences metabolism, glucose homeostasis etc. * This results in the release of _Somatomedins_ from the liver ( = I_nsulin-like growth factor-1 or IGF-1_) * These hormones stimulate growth of skeletal muscle, cartilage and many other tissues. * The Somatomedins then act on the brain resulting in inhibitory process. The Periventricular nucleus releases GH-Inhibiting hormones into the anterior lobe which regulates the synthesis of Somatomedins

Question 33

What is another name for Somatomedins?

Answer 33

= Insulin-like growth factor-1 or IGF-1

Question 34

What is another name for lGF-1?

Answer 34

**Somatomedins** from the liver ( = Insulin-like growth factor-1 or IGF-1)

Question 35

What is the role of prolactin and where is it produced/released?

Answer 35

Prolactin regulates lactation (released from the Anterior pituitary) Regulates milk _production_ but also involved in its _release_.

Question 36

What is the role of oxytocin and where is it produced/released?

Answer 36

Hypothalamic hormone, but released from the posterior pituitary Responsible for **milk ejection**

Question 37

Describe the processes involved in prolactin (normally)

Answer 37

Prolactin itself can regulate its own production and release It is synthesised in the _Anterior Pituitary_, it will act on the _hypothalamus_ (_Tuberoinfundibular dopamine neurons_), which will promote the release of dopamine and will have a _negative feedback_ on its own production.

Question 38

Prolactin s synthesised in the Anterior Pituitary, it will act on the ________ neurons.

Answer 38

It is synthesised in the Anterior Pituitary, it will act on the hypothalamus (Tuberoinfundibular dopamine neurons),

Question 39

Describe the adaptive changes of prolactin secretion during pregnancy and lactation

Answer 39

(Not well understood)- but basically trying to over-ride the negative feedback to a positive one. 1. During pregnancy, the placenta releases _Placental lactogens_ as additional source of lactogen, bypassing feedback. 2. _Less dopamine secretion_ in response to prolactin secretion from theTuberoinfundibular dopamine neurons). 3. Powerful _prolactin-releasing stimulus_ released by the suckling stimulus (when the baby sucks on the breast). \*not proven 4. Increased _prolactin transport_ to the brain * One of the most improtant regulator of secretion of prolactin is **Estrogen** (E2). * It i_ncreases the number of lactotrophs_, r_egulates lactotroph responsiveness_ and acts on the _Tuberoinfundibular dopmaine neurons_. * During pregnancy there is an increase in release of estrogen

Question 40

Describe the estrogen feedback on the Gonadotropin-releasing hormone (GnRH) neuronal network

Answer 40

GnRH neurons are scattered around the hypothalamus. * The GnRH is released into the _Anterior pituitary_, which releases FSH and LH * _FSH and LH_ work on the gonads(e.g. ovaries, testes), which produces estrogen in response * The estrogen then inhibits the _GnRH neurons_

Question 41

What does FSH and LH stand for?

Answer 41

Luteinizing hormone (LH) andfollicle-stimulating hormone (FSH) are called gonadotropin

Question 42

What are LH and FSH collectively called?

Answer 42

Luteinizing hormone (LH) andfollicle-stimulating hormone (FSH) are called **gonadotropin**

Question 43

Describe the hormonal control fo the **male** The hypothalamic–pituitary–gonadal axis (HPG axis)

Answer 43

1. Hypothalamus secretes _Gonadotrophin releasing hormones (GnRH)_ 2. _GnRH_ (in hypothamic-putuitary portal vessels) 3. Anterior pituitary secretes _FSH and LH_ * FSH acts on the **Sertoli sells**, which: * stimulates _spermatogenesis_ * Produces _inhibin_ (which inhibits release of FSH (only) from the Anterior pituitary) * LH acts on the **Leydig cells,** which: * Stimulates the release of _testosterone_ * Testosterone has a local, excitatory effect on the sertoli cells * Testosterone also _inhibits the release of LH_ (only) from the Anterior pituitary cells. * Testosterone also _inhibits the release of GnRH_ from the hypothalamus * The reproductive tract and other organs also respond to testosterone.

Question 44

Describe the role of FSH in males

Answer 44

FSH acts on the _Sertoli_ sells, which: * stimulates spermatogenesis * Produces inhibin (which inhibits release of FSH (only) from the Anterior pituitary)

Question 45

Describe teh role of LH in males

Answer 45

LH acts on the _Leydig cells_, which: Stimulates the release of _testosterone_ * Testosterone has a local, _excitatory effect on the sertoli cells_ * Testosterone also in_hibits the release of LH_ (only) from the Anterior pituitary cells. * Testosterone also _inhibits the release of GnRH f_rom the hypothalamus * The reproductive tract and other organs also respond to testosterone.

Question 46

Describe the Menstrual Cycle

Answer 46

* **_Follicular_** phase * Increased level of _estrogen_ will go from a _negative feedback loop to a positive one._ * The positive feedback-loop of estrogen will cause a surge in _LH and FSH_ * Increased levels of _LH and FSH will trigger ovulation._ * **_Luteal_** phase * Due to the formation of the _corpus luteum_, the levels of _protestone and estrogen will rise_ * If there's a _preganancy_, the estrogen and progesterone will _remain high_ and will maintain the pregnancy. If not this will _fall_.

Question 47

Describe the principal steroidogenic pathways in the ovarian follicle

Answer 47

The LH and the FSH will also act ont he Granulosa cell

Question 48

Describe the Estrogen feedback on GnRH neuronal network

Answer 48

1. _Estrogen_ produced by the _Developing follicles_ will have a _negative_ feedback on the LH as well as the GnRH 2. _Estrogen_ produced by the _Dominant follicles_ will have a _positive_ feedback on the LH and the GnRH. 3. The _Progesterone_ released by the Corpus Luteum will result in a _negative_ feedback to reduce the release of FSH from the Anterior pituitary and the GnRH.

Question 49

Briefly describe the role of contraception on the GnRH neuronal network

Answer 49

They are either: _estrogen and progesterone_ or just _progesterone_. _Estrogen_ will _block the release of FSH and LH._If there's no surge of FSH and LH, there is _no ovluation_. _Progesterone_ can act on the c_ertical mucous_ to stop the sperm from reaching the uterus. It also act on the _endometrium_ so if there's ovulation, the egg will not plant because the uterus is not ready. Can put people at risk of thrombo

Question 50

Briefly describe the findings of Kwakosky's study

Answer 50

1. You cannot explain how the system works by the classical post-estrogen feedback cycle theory. 2. There are effects of GnRH neuron specific deletion of CREB on the estrogen negative feedback mechanisms. 3. There was also decreased spine density of GnRH neurons in CREB knockout mice.

Question 51

Describe the Kisspeptin regulation of GnRH neuron activity

Answer 51

You cannot explain how the system works by the classical post-estrogen feedback cycle theory. Kisspeptin neurons are essential in initiating puberty. ("puberty begins with a kiss) By changing the firing rate of the Kisspeptin neurons, you can change the LH and FSH release.

Question 52

Case Report 1 Ovarian function tests showed that LH, FSH and estradiol are extremely low. Diagnosed with _Severe hypogonadotropic hypogondaism_ (HH) MRI suggests that there is a _mass_ lesion extending from the pituitary fossa to the suprasellar area Patient also had bitemporal hemianopia.

Answer 52

**Hyperpituitary-acromegaly** -when serum somatotropin is very high.

Question 53

Case Report 2 8 year old girl Premature breast development with slow progression had been observed since birth High estradiol levels No abnormality in the ovaries Treated with GnRH analogue

Answer 53

Mutation in proline for Arginine (the receptors of the upstream neurons- _Kisspeptin_ were abnormal) Nonconstiutive receptor activation, reduction of ther ate of GPR54 desensitization Results in: increased, prolonged cellular response and hence the release of an _increased amplitude pulse of GnRH_ in response to _kisspeptin stimulation._

Question 54

Case Report 3 Serious hyposmia (Performance was under the 10th percentile) Low FSH, LH and estrogen Amenorrhea probably because of primary HH, the impaired glucose tolerance and hyperinsulinism Bone desnity problems indicate......

Answer 54

Kallmann syndrome (GnRH deficiency)

Question 55

What are pre pubertal Testosterone, Estradiol and LH/FSH levels?

Answer 55

Testosterone: * \<10-20ng/dL Estradiol * \<5-10pg/ml LH/FSH * \<1 IUl/L

Question 56

What is estradiol?

Answer 56

Estradiol is a _form of the hormone estrogen_

Question 57

What are the normal Testosterone, Estradiol, LH and FSH level in ADULT MALES

Answer 57

* Testosterone * 280-1,000 ng/dL * Estrodiol * 10-40 pg/ml * LH * 0.7-7.9 IU/L * FSH * 1.5-12.4 IU/L

Question 58

What are the normal Testosterone, Estradiol, LH and FSH level in ADULT FEMALES

Answer 58

* Testosterone * 8-48ng/dL * Estradiol * mid-follicular phase: 27-123pg/ml * preovulatory phase: 96-436pg/ml * pregnant women in 3rd trimester: 6137-3460pg/ml * post-menopause: \<30pg/ml * LH * mid-follicular phase: 1.9-12.5 IU/L * preovulatory phase: 8.7-76.3 IU/L * Luteal phase: 6137-3460pg/ml * pregnant women: \<1.5 IU/L * FSH * mid-follicular phase: 1.37-9.9 IU/L * preovulatory phase: 6.7-17.2 IU/L * Luteal phase: 1.09-9.2 IU/L * pregnant women: \<2 IU/L