Introduction to the Hypothalamic-Pituitary Axis Flashcards

Question

_Hypothalamic releasing hormones_ * ... releasing hormone (TRH) * ... AA, isolated in 1969 * Stimulates ... secretion

Answer 1

* **thyrotropin** releasing hormone (TRH) * **3** AA, isolated in 1969 * Stimulates **TSH** secretion

Answer 2

* GHRH (**growth hormone** releasing hormone) * **44** AA, **G** protein receptor secretin family * Stimulates **GH** secretion

Answer 3

* hypothalamus has neurosecretory cells that secrete **releasing** hormones * these travel down the **portal** circulation in the pituitary **stalk** to the **anterior** pituitary (where they have their action) * neurosecretory cells also secrete posterior pituitary hormones * posterior pituitary has more **neurological** tissue

Answer 4

Hormones from the hypothalamus are delivered to the **anterior** pituitary via the hypothalamic-**hypophyseal** portal system. It is **sinusoidal** and has **pores** which allows free access and movements of these peptides.

Answer 5

* hypothalamus cells - **releasing** and **inhibiting** hormones - flow down **portal** system - to the **anterior** pituitary - cause this to produce or inhibit **anterior** pituitary hormones * enter **systemic** circulation and travel to distal **target** tissues and have affect * cells in hypothalamus also have **vasopressin** (ADH) and **oxytocin** - into **posterior** pituitary - directly into **systemic** circulation

Answer 6

The **hypothalamic-pituitary** axis (HPA axis) is an interactive neuroendocrine unit comprising of the **hypothalamus**, the **pituitary** gland, and the **ad****renal** glands. * The HPA axis plays key roles in basal **homeostasis** and in the body's response to **stress**

Answer 7

* For **Cortisol** Regulation (main glucocorticoid) * **Corticotropin**-releasing hormone (CRH) is secreted by the hypothalamus * CRH travels in the blood to anterior pituitary - specifically to corticotrophs * These produce **ACTH** * This is released into the bloodstream and travels to the adrenal glands, where it binds to specific receptors on the adrenal **cortex**. * The binding of ACTH to the receptors on the adrenal cortex stimulates the release of **cortisol** into the bloodstream. * **Negative feedback** mechanism

Answer 8

* **Thyrotropin**-releasing hormone (TRH) is released from the hypothalamus * TRH travels in the blood to anterior pituitary - to thyrotrophs * Production/release of **thyroid stimulating hormone - TSH** * This is released into the bloodstream and travels to the thyroid gland * Stimulatory effect to promote production of both **T3** and **t4** * **negative feedback mechanism**

Answer 9

* GnRH (**gonadotropin** releasing hormone) is released from the hypothalamus * flows through the gonadotropes in pituitary * **FSH** and **LH** are both produced * direct effect to stimulate either testes to produce **testosterone and sperm** or the ovaries to make **oestrogen** and **eggs**

Answer 10

* GHRH (known as **growth hormone releasing hormone**) * Somatostatin is the **inhibitor** (these both act in concert to have a tonic control of secretion of growth hormone) * Secretion of growth hormone * Acts on the **liver** (part of body?) to make a hormone called **IGF-**1 * mediates it's effects

Answer 11

* **dopamine** is the main controller of prolactin secretion and acts in a **negative** manner * The **dopamine** agonist cause **reduction** in prolactin whereas **dopamine** antagonist **raise** prolactin levels

Answer 12

* stimulus on the **hypothalamus** * causing **trophic** hormone to be released * flows to **anterior** pituitary * **trophic** hormone produced * travels in **bloodstream** to a distal endocrine system/target tissue * creates **additional** hormones * long loop negative feedback from hormone and also the short loop negative feedback from hormone (e.g long = **cortisol** acting on anterior pituitary and hypothalamus, also short = **ACTH** acting on hypothalamus in addition)

Answer 13

1. Thyroid stimulating hormone (TSH) - affects thyroid 2. Adrenocorticotropic hormone (ACTH) - affects adrenals - only affects cortisol production (aldosterone etc not effected by ACTH) 3. Growth hormone (GH) - multitude of effects but direct effect on liver to make IGF-1 4. Follicle stimulating hormone (FSH) - act on gonads in girls and boys 5. Luteinizing hormone (LH) - act on gonads in girls and boys 6. Prolactin (Prl) - acts on the breasts and also acts as contraceptive - dampens down the ovaries

Answer 14

1. Arginine Vasopressin (AVP) - ADH 2. Oxytocin

Answer 15

1. **Somatotropes** (**50**% of anterior lobe cells) - these synthesize **growth** hormone - a polypeptide 2. **Lactotropes** (**10-****20**% of cells) - these synthesize**prolactin** - a polypeptide 3. **Corticotropes** (**5-10**% of cells) - these synthesize **ACTH** - endorphin, peptide varying from 31-20 AA 4. **Thyrotropes** (**5**% of cells) - Produce **thyrotropin** known as **TSH** - a glycoprotein 5. **Gonadotropes** (**10-15**% of cells) - Produce **Luteinizing** hormone and **Follicle stimulating** hormone - both glycoproteins

Answer 16

Structure of anterior lobe cells

Answer 17

Electron micrograph of a somatograph (growth hormone secreting cell)

Answer 18

* hypothalamus - **precursor** hormones produced * **pituitary** hormones * **distal** site - hormones secreted here

Answer 19

* Molecular weight of **22,000** * bound to **high** **affinity** bound protein and **low** **affinity** bound protein * half life varies from **6 to 20 minutes** * **pulse to pulse secretion** * **predominantly secreted at night** * **acts on liver to produce IGF1**

Answer 20

As well as acting on the liver, **growth** hormone also has a major effect on a lot of bones and structural tissues. It also plays a role in adults to keep **muscle** in good shape and for regeneration after **exercise**

Answer 21

* Prolactin is a **199** amino acid peptide, synthesised in the **lactotrophe** cells of the anterior pituitary * major function of prolactin is **milk** production - what stimulates it's ejection? - **oxytocin** * release is tonically inhibited by **dopamine (PIH)** * inhibits **gonodal** function (nature is contraceptive) * **negative** influence

Answer 22

* Regulation of thyroid synthesis and secretion via hypothalamic-pituitary-thyroid axis * Hypothalamus - **TRH** released - **anterior** pituitary - **TSH** - thyroid - **T3** and **T4** produced - also growth of thyroid - **negative** feedback on the hypothalamus and the anterior pituitary

Answer 23

* Adrenal medulla - does ACTH affect it? - **NO** 1. Zona **glomuerulosa** - **mineralocorticoids** 2. Zona **fasciculata** - **glucocorticoids** 3. Zona **reticularis** - **androgens** * **ACTH only affects glucocorticoid production (****cortisol)**

Answer 24

Cortisol has a **diurnal** variation - usually high in the **morning** and low at **night** * stressful stimulus causes cortisol release

Answer 25

* Long polypeptides (\>**100** AA) bound to one or more **carbohydrate** group

Answer 26

* control the **menstrual** cycle * **oestrogen** formation and formation of **eggs** * LH more to do with production of **oestrogen** and FSH more to do with production of **eggs** * both needed to develop these things

Answer 27

* The menstrual cycle is orchestrated by the **endocrine** system through the complex interaction of the hypothalamus, pituitary and gonads (**hypothalamic-pituitary-gonadal axis**). The entire menstrual cycle lasts around **28** days, with the cycle beginning on the first day of menstruation and **ovulation** occurring at approximately day 14. * Surge of FH & LH around **ovulation**

Answer 28

* FSH and LH affects production of **sperm** and **testosterone** * LH more to do with productioo of **testosterone** * FSH more to do with production of **sperm**

Answer 29

* Comprised of the endings of **axons** from cell bodies in the **hypothalamus** (**supraoptic** and **paraventricular**) * Axons pass from the **hypothalamus** to the posterior pituitary via the **hypothalamohypophysial** tract * Posterior pituitary hormones are synthesized in the cell bodies of neurons in the **supraoptic** and **paraventricular** nuclei

Answer 30

* Hormones synthesized in the hypothalamus are transported down the axons to the endings in the **posterior** pituitary * Hormones are stored in **vesicles** in this part of the pituitary until release into the circulation * Principal hormones are **vasopressin (ADH)** and **oxytocin**

Answer 31

Synthesis, storage and release of posterior pituitary hormones

Answer 32

Two embryological origins for the pituitary gland - the **adenohypophysis** and the **neurohypophysis**

Answer 33

* outgrowth from the **hypothalamus** * median **eminence** - nerve endings and capillaris * **pars** **nervosa** (posterior or nerual lobe) - contains nerve endings and capillaries

Answer 34

Neurosecretory nerve terminals in contact with a capillary in the posterior lobe

Answer 35

The two posterior hormones are small **peptides** that are really structural in nature

Answer 36

* **Antidiuretic actions** * increases **permeability** of the **collecting** **ducts** to water * V**2** receptors * **Vasopresser actions** * **constricts** vascular **smooth** muscle cells * V**1** receptors, non-**hormonal**

Answer 37

* ADH causes urine to become more **concentrated** * more water is brought into **circulation**

Answer 38

* **Low** BP/circulating volume * **ADH** then produced * increases water **production,** increase **BP**

Answer 39

* Breast-feeding * contracts the **myoepithelial** cells of the **alveoli** * classic **neuroendocrine** reflex * childbirth (**parturition**) * in late pregnancy, uterine smooth muscle (**myometrium**) becomes sensitive to oxytocin * **positive** feedback mechanism

Answer 40

Positive feedback mechanism

Answer 41

Oxytocin is a **G** protein linked receptor causes **calcium** influx - causes contraction of smooth muscle in **endometrium or breast**

Answer 42

* *Hypothalamic (hypothalamic or pituitary stalk disease) vs. primary pituitary disease* * _**Acquired** defects_: Tumors (inc pit **adenomas**), trauma, inflammatory/infiltrative, vascular (inc. Apoplexy) * _**Congenital** **embryopathic** defects_: **Killman's** syndrome, pituitary Aplasia, Anencephaly, Midline defects (rare) * _**Genetic** Defects_: Hypothalamic/Pituitary Hormone gene defects and hormone receptor gene defects (Very rare)

Answer 43

* Mass effects include **headaches** and changes in **visual** field * Endocrine effects: * **hypo**pituitarism: * **hyper**pituitarism:

Answer 44

* progressive loss of **anterior** **pituitary** function: first hormones to go = **FSH/LH** and **GH**; **TSH**; **ACTH** * Hypopituitarism with **Diabetes** **Insipidus** is suggestive of hypothalamic etiology

Answer 45

Pituitary tumour

Answer 46

* most common = prolactin tumours * second most common = non-functioning tumors * relatively common = GH tumours, ACTH tumors * least common = FSH/LH * Very rare = TSH tumors

Answer 47

* Microadenomas are \<**10mm** * Macroadenomas are \>and including **10mm** * majority are monoclonal and not **malignant** * may or may not be **functional** * **mass** effects and **hypopituitarism** may be present irrespective of functional status * functioning (Secretes **hormones**) vs. non-functioning

Answer 48

* **Prolactinomas:** Produce too much prolactin * Produces galactorreah, reduced **gonodal** function * **ACTH** secreting tumours: produce too much ACTH - too much cortisol = **cushing's** syndrome * centropetal **obesity**, **thin** skin, osteoporosis, **diabetes** * **GH** secreting: produce too much growth hormone - **acromegaly** * FSH/LH secreting: rare * **hypersecretion** syndromes * TSHomas: TSH secreting - very rare * **leads to thyrotoxicosis**

Answer 49

* **History** - symptoms of hormone excess or deficiency * **examination** - signs of hormone excess or deficiency * basal hormone result s- pituitary hormones e.g. **prolactin**, ACTH, GH and downstream hormones e.g. **cortisol**, IGF-1 * **Stimulated** secretion - to distinguish normal from abnormal * **Visual** fields * **Imaging** e.g. MRI (CT - first way historically, MRI better)

Answer 50

* Give **insulin** * Blood glucose **fall** - below **2** = pituitary churns out **hormones** to raise this level * If you induce **hypoglycaemic** episode = max response from pituitary, checks it's **response**

Answer 51

* 2 catheters into **vein** supplying pituitary, either side * give **CRH** - cortisol releasing hormone * Causes **ACTH** production from pituitary * ACTH secreting adenoma = **greater** release of ACTH * See in figures if much brisker response on either side of the pituitary - shows what **side** the tumour is on

Answer 52

* Optic **chiasm** - nerves cross above **pituitary** - lesion pressing on this means you get a **Bitemporal** **hemianopsia** * lose vision on **outside** of both eyes * only place that causes this - characteristic of a pituitary tumour pressing on optic chiasm * tells you exactly where lesion is

Answer 53

* CT scan of pituitary

Answer 54

MRI of pituitary

Answer 55

MRI of pituitary adenoma touching the optic chiasm