Lecture 1 and 2 Introduction and Hypothalamus/pituitary (I & II) Flashcards
What does the hypothalamus do?
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
What does the Pituitary Gland do?
Secretes multiple hormones that regulate the endocrine activities of the adrenal cortex, thyorid gland and reporductive organds, and a hormone that stimulates melanin production.
What part of the brain is diencephalon part of?
What brain structures make up the diencephalon?
Part of the forebrain
Made up of:
- Thalamus
- Hypothalamus
- Epithalamus
How does the Diencephalon develop?
Hypothalamus develops from the hindmost part of the forebrain – the diencephalon.
Describe the development of the pituitary gland
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.
What is another name for “Anterior Pituitary”
adenohypophysis
What is another name for “Posterior Pituitary”?
Neurohypophysis
Reproduction is controlled by a ___________
Reproduction is controlled by a hierarchical arrangement of endocrine glands with the
hypothalamus as the ‘master regulator’.
Describe the basic hormonal feedback control of the hypothalamus and antieror pituitary
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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Hormones secreted by the hypothalamus are produced by _____
Hormones secreted by the hypothalamus are produced by neurons aggregated into ‘nuclei’.
Hypothalamic hormones are released from axon terminals work either _______ or ______
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.
Feed-back loops from target organs control release of hormones from the hypothalamus.
Feed-back is mostly ______, but is_____ during _______
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.
Secretion of hypothalamic hormones is ______, that is they are released_______
Secretion of hypothalamic hormones is pulsatile, that is they are released in d_iscrete bursts_
Where is the hypothalamus?
What structures surround the hypothalamus and the pituitary gland?
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
Name the major nuclei of the hypothalamus
1) Paraventricular (PVN)
2) Supra-optic (SO)
3) Parvicellular
What are the 2 parts of the pituitary (both names for both)
Pituitary gland consists of 2 lobes
1) Anterior (Adenohypophysis)
2) Posterior (Neurohypophysis)
Describe the Blood supply to the hypothalamus and the pituitary
- Superior hypophyseal artery
- Anterior hypophyseal veins
- Inferior hypophyseal artery
- Posterior hypophyseal veis
- Primary plexus of hypophyseal portal system
- Hypophyseal portein veins
- Secondary plexus of hypophyseal portal system
- Capillary plexus of infundibular process
How does the hypothalamus interact with the pituitary gland?
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.
The capillary networks in the median emience are supplied by the ____________
The capillary networks in the median emience are supplied by the Superior hypophyseal artery.
Neurons from the Supraoptic nuclei and Paraventricular Nuclei release….
-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.
What hormones are released from the hypothalamus and released via the hypophysial portal system?
- Gonadotrophin-releasing hormone
- Thyrotropin-releasing hormone
- Corticotropin-releasing hormone
- Prolactin-releasing hormone
- Prolactin-inhibting hormone
- Growth hormone-releasing hormone
- Somatostatin
What hormones are released from the pituitary? (6)
- Follicile-stimulating hormone
- Luteinizing hormone
- Thyroid-stimulating hormone (thyrotopin)
- Adrenocorticotropic hormone
- Polactin
- Growth hormone
Which is one anterior and which one is posterior pituitary?
And why?
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)
What are these?
Where are they found?
Anterior pituitary
Pink: Acidophils (50% are somatotrophs and 20% are mammotrophs)
Purple: Basophils (20% Corticotrophs, 5% Thyrotrophs and 5% Gondaotrophs)
Describe the Histology of the Anterior Pituitary
- Pink: Acidophils (50% are somatotrophs and 20% are mammotrophs)
- Purple: Basophils (20% Corticotrophs, 5% Thyrotrophs and 5% Gondaotrophs)
What are the different types of acidophils?
Acidophils (50% are somatotrophs and 20% are mammotrophs)
What are the different types of Basophils?
Purple: Basophils (20% Corticotrophs, 5% Thyrotrophs and 5% Gondaotrophs)
What are these cells and what do they produce?
Describe the Hypothalamic and Pituitary hromones and some effects on the target tissues
Describe the process of release of Growth Hormone
- 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
What is another name for Somatomedins?
= Insulin-like growth factor-1 or IGF-1
What is another name for lGF-1?
Somatomedins from the liver ( = Insulin-like growth factor-1 or IGF-1)
What is the role of prolactin and where is it produced/released?
Prolactin regulates lactation (released from the Anterior pituitary)
Regulates milk production but also involved in its release.
What is the role of oxytocin and where is it produced/released?
Hypothalamic hormone, but released from the posterior pituitary
Responsible for milk ejection
Describe the processes involved in prolactin (normally)
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.
Prolactin s synthesised in the Anterior Pituitary, it will act on the ________ neurons.
It is synthesised in the Anterior Pituitary, it will act on the hypothalamus (Tuberoinfundibular dopamine neurons),
Describe the adaptive changes of prolactin secretion during pregnancy and lactation
(Not well understood)- but basically trying to over-ride the negative feedback to a positive one.
- During pregnancy, the placenta releases Placental lactogens as additional source of lactogen, bypassing feedback.
- Less dopamine secretion in response to prolactin secretion from theTuberoinfundibular dopamine neurons).
- Powerful prolactin-releasing stimulus released by the suckling stimulus (when the baby sucks on the breast). *not proven
- 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
Describe the estrogen feedback on the Gonadotropin-releasing hormone (GnRH) neuronal network
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
What does FSH and LH stand for?
Luteinizing hormone (LH) andfollicle-stimulating hormone (FSH) are called gonadotropin
What are LH and FSH collectively called?
Luteinizing hormone (LH) andfollicle-stimulating hormone (FSH) are called gonadotropin
Describe the hormonal control fo the male The hypothalamic–pituitary–gonadal axis (HPG axis)
- Hypothalamus secretes Gonadotrophin releasing hormones (GnRH)
- GnRH (in hypothamic-putuitary portal vessels)
- 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.
- Stimulates the release of testosterone
- FSH acts on the Sertoli sells, which:
Describe the role of FSH in males
FSH acts on the Sertoli sells, which:
- stimulates spermatogenesis
- Produces inhibin (which inhibits release of FSH (only) from the Anterior pituitary)
Describe teh role of LH in males
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.
Describe the Menstrual Cycle
-
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.
Describe the principal steroidogenic pathways in the ovarian follicle
The LH and the FSH will also act ont he Granulosa cell
Describe the Estrogen feedback on GnRH neuronal network
- Estrogen produced by the Developing follicles will have a negative feedback on the LH as well as the GnRH
- Estrogen produced by the Dominant follicles will have a positive feedback on the LH and the GnRH.
- 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.
Briefly describe the role of contraception on the GnRH neuronal network
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
Briefly describe the findings of Kwakosky’s study
- You cannot explain how the system works by the classical post-estrogen feedback cycle theory.
- There are effects of GnRH neuron specific deletion of CREB on the estrogen negative feedback mechanisms.
- There was also decreased spine density of GnRH neurons in CREB knockout mice.
Describe the Kisspeptin regulation of GnRH neuron activity
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.
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.
Hyperpituitary-acromegaly
-when serum somatotropin is very high.
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
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.
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……
Kallmann syndrome (GnRH deficiency)
What are pre pubertal Testosterone, Estradiol and LH/FSH levels?
Testosterone:
- <10-20ng/dL
Estradiol
- <5-10pg/ml
LH/FSH
- <1 IUl/L
What is estradiol?
Estradiol is a form of the hormone estrogen
What are the normal Testosterone, Estradiol, LH and FSH level in ADULT MALES
- 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
What are the normal Testosterone, Estradiol, LH and FSH level in ADULT FEMALES
- 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
