10 - Hypothalamic and Pituitary Relationships and Biofeedback Pt. I Flashcards
The pituitary gland (hypophysis) is composed of the anterior pituitary (adenohypophysis) which is the _______ portion, and the posterior pituitary (neurohypophysis) which is the ________ portion.
Epithelial
Neural
This is the physical connection between the hypothalamus and the pituitary gland.
Hypophysial Stalk
Due to its anatomical location, tumors in the pituitary gland will expand and put pressure on the _______ nerves because of its close proximity to the _______ ______. It causes visual problems and dizziness.
Optic
Optic Chiasm
The posterior pituitary is derived from neural tissue. It is a collection of axons and nerve terminals whose cell bodies are located in the Hypothalamus within the ________ ________ and ________ ________.
Supraoptic Nucleus (SON) Paraventricular Nucleus (PVN)
What neuropeptides are secreted from the SON and PVN?
ADH (from SON)
Oxytocin (from PVN)
The communications between the hypothalamus and the anterior pituitary are ________ and ________.
Neural
Hormonal
***Remember, the connections between the hypothalamus and posterior pituitary are ONLY neural!
The anterior pituitary is a collection of endocrine cells derived from the primitive foregut. It secretes…
ACTH TSH FSH LH GH Prolactin
How is the hypothalamus connected to the anterior pituitary?
Via the Hypothalamic-Hypophysial Portal blood vessels
The Hypothalamic-Hypophysial Portal system can transport hypothalamic-releasing hormones or release-inhibiting hormones DIRECTLY to the anterior pituitary in (LOW/HIGH) concentrations. Hormones do not appear in (LOW/HIGH) concentrations in systemic circulation.
High
High
Hormone families of the anterior pituitary are organized by structural and functional homology. What are these families?
ACTH family — Corticotrophs secrete ACTH
TSH, FSH, LH family — Thyrotrophs secrete TSH; Gonadotrophs secrete FSH and LH
GH, Prolactin family — Somatotrophs secrete GH; Lactotrophs secrete Prolactin
What hormone from the hypothalamus targets Thyrotrophs in the anterior pituitary to secrete TSH?
TRH (Thyrotropin Releasing Hormone)
What hormone from the hypothalamus targets Corticotrophs in the anterior pituitary to secrete ACTH?
CRF (Corticotropin Releasing Factor)
What hormone from the hypothalamus targets Gonadotrophs in the anterior pituitary to secrete LH and FSH?
GnRH (Gonadotropin Releasing Hormone)
What hormone from the hypothalamus targets Somatotrophs in the anterior pituitary to secrete GH?
GHRH (Growth Hormone Releasing Hormone)
What hormone from the hypothalamus targets Somatotrophs in the anterior pituitary to inhibit the secretion of GH?
Somatostatin (GHIH - Growth Hormone Inhibiting Hormone)
What hormone from the hypothalamus targets Lactotrophs in the anterior pituitary to secrete Prolactin?
TRH (elevated)
***Remember, Prolactin is the only hormone that under normal conditions is being inhibited.
What hormone from the hypothalamus targets Lactotrophs in the anterior pituitary to inhibit secretion of Prolactin?
PIF (dopamine)
Activity of endocrine axes are maintained around a set point that is maintained by _______ _______ mechanisms.
Negative feedback
Hypothalamic hormones are often secreted in a pulsatile manner and are entrained to _______ _______.
Circadian rhythms
What is a primary endocrine disorder?
Low or high levels of hormone due to defect in the peripheral endocrine gland.
What is a secondary endocrine disorder?
Low or high levels of hormone due to defect in the pituitary gland.
What is a tertiary endocrine disorder?
Low or high levels of hormone due to defect in the hypothalamus.
What are the anterior pituitary axes?
Hypothalamic-Pituitary-Gonad (HPG) Hypothalamic-Pituitary-Liver Hypothalamic-Pituitary-Prolactin Hypothalamic-Pituitary-Thyroid Hypothalamic-Pituitary-Adrenal
Describe the HPG axis.
Hypothalamus secretes GnRH, which stimulates Gonadotrophs in the anterior pituitary to release LH and FSH.
In females, LH induces Theca cells to produce Androgens and FSH induces Granulosa cells to produce Progesterone and Estrogen.
In males, LH induces Leydig cells to produce Testosterone and FSH induces Sertoli cells to produce Androgen-binding protein and spermatogenesis.
What is the negative feedback mechanisms for the HPG axis in males?
Testosterone (from Leydig cells) will inhibit the release of LH from the anterior pituitary, and inhibit the release of GnRH from the hypothalamus.
Inhibin is secreted from Sertoli cells to inhibit the release of FSH from the anterior pituitary.
What is the negative feedback mechanisms for the HPG axis in females?
Estrogen and Progesterone (from Granulosa cell) will inhibit the release of LH and FSH from the anterior pituitary, and inhibit the release of GnRH from the hypothalamus.
Inhibin is secreted from Granulosa cells to inhibit the release of FSH from the anterior pituitary.
For females, at mid-cycle (menstrual) there is positive feedback pathways for the HPG axis. What are these pathways?
Estrogen (from Granulosa cell) stimulates further secretion of LH and FSH from the anterior pituitary, and further secretion of GnRH from the hypothalamus.
A normal menstrual cycle depends on what hormones?
LH
FSH
This is a rare disease characterized by excessive growth of soft tissue, cartilage, and bone in the face, hands, and feet. It develops very gradually and may not be recognized until it has been present for many years. It’s caused by prolonged and excessive secretion of growth hormone (GH) in adult life.
Acromegaly
Growth Hormone (GH), also called __________, is produced by somatotropes and targets the liver and bone.
Somatotropin
GH has a GH receptor (GHR) linked to ________ signaling.
JAK-STAT
GH is inhibited by _________ and ________, which is part of the negative feedback.
Somatostatin
IGF-1
Extreme energy deficits (anorexia nervosa or starvation), extreme exercise, and depression can inhibit ________ function.
GnRH
***This is why a lot of times anorexic women or women that exercise way too much won’t have periods.
What can stimulate GH?
Fasting/hunger/starvation Hypoglycemia Hormones of puberty Exercise Sleep Stress
What are the 3 direct actions of GH?
1) Growth (hypertrophy)
2) Cell reproduction (hyperplasia)
3) Metabolism
This is the term for increased size/volume of cells, an example being increase in bone thickness. This is involved with the direct action of growth from GH.
Hypertrophy
This is the term for an increased number of cells or proliferation rate via mitosis, an example being an increase in bone length. This is involved with the direct action of cell reproduction from GH.
Hyperplasia
For the direct action of metabolism from GH, there is an increase in _________ and ________ breakdown for energy. There is also an increase in ________ synthesis.
Glycogen
Fat
Protein
For GH, the majority of growth is via the ________ method. It has a tropic function and signals to the liver to produce _______. It targets almost every cell in the body, stimulates hypertrophy and hyperplasia.
Indirect
IGF
Describe the Hypothalamic-Pituitary-Growth Hormone (HPGh) axis.
The hypothalamus releases GHRH or GHIH (somatostatin), which induces the secretion of GH (somatotropin) from the anterior pituitary. GH travels to the liver and induces its secretion of IGF and IGF-1 (somatomedin C).
What is the negative feedback mechanisms of the HPGh axis?
IGF-1 (from liver) inhibits the release of GH from the anterior pituitary, and promotes the secretion of GHIH from the hypothalamus.
GH from the anterior pituitary inhibits the release of GHRH from the hypothalamus.
What does a growth hormone insensitivity look like in the HPGh axis?
There is a high level of GH, and the liver is not responding to it. This means there is less IGF-1 being produced. Less IGF-1 means there is less inhibition of GH, which further increases its levels.
***Primary endocrine deficiency because its an issue with a peripheral endocrine gland (the liver)
What does a secondary deficiency look like in the HPGh axis?
There is low levels of GH because of an issue within the pituitary. This results in less production of IGF-1.
***With less IGF-1, you would think there would be more GH because there is nothing to inhibit it, but since there is a defect within the pituitary then the GH isn’t being produced like it should be.
What does a tertiary deficiency look like in the HPGh axis?
There is low levels of GHRH and Ghrelin (fed vs. fasting states) because of an issue with the hypothalamus. This results in less production of GH and IGF-1.
_________ occurs BEFORE closure of bone epiphyses due to IGF-1 stimulated long bone growth. It’s from an excess in GH.
Gigantism
_________ occurs AFTER closure of bone epiphyses due to promotion of growth of deep organs and cartilaginous tissue. It’s from an excess in GH.
Acromegaly
Explain what happens with growth promoting factors in the fed state.
When you have adequate carbohydrate intake and protein intake, then there is plenty of insulin and amino acid availability. GH is secreted and the liver will produce IGF-1. The IGF-1 induces the actions of mitogenesis, lipolysis, and differentiation (i.e., increased osteoblasts, collagen, and bone matrix).
***This is normal, what we want to happen.
Explain what happens in unfavorable growth conditions, such as when carbohydrate intake is adequate, protein intake is not.
If carbohydrate intake is adequate there is plenty of insulin available, but if protein intake is insufficient then there is not enough amino acid availability. This results in the inhibition of GH, which causes the liver to not produce IGF-1. Lipogenesis and carbohydrate storage will occur, causing weight gain.
***If you’re eating a bunch of carbs and no protein you’re gonna be a chunky monkey.
Explain what happens with growth promoting factors in the fasted state.
In this state, you have inadequate carbohydrate intake resulting in low levels of insulin availability. Protein intake is adequate, making availability of amino acids. GH levels will increase, and the liver will produce IGF-1. This results in lipolysis, ketogenic metabolism, and being diabetogenic. Peripheral metabolism shift to use lipids as your energy source.
***This is what happens when you think of the keto diet. You eat a ton of protein and fat, but low carb. You burn a ton of fat and it makes you lose weight.
In the fasted state, GH promotes lipolysis but can also promote insulin insensitivity. GH will raise blood glucose by decreasing peripheral glucose uptake and stimulating hepatic ___________.
Gluconeogenesis
***This is not pathological, insulin levels are just low.
If you have elevated serum GH and IGF-1 levels, then you will have failure to suppress GH production in response to an oral load of _________. This is a very sensitive test for acromegaly!
Glucose
GH secretion fluctuates throughout the day, primarily during ________. ________ disturbances perturb GH secretion, and GH will peak with _________.
Sleep
Sleep
Exercise
T/F. GH stops secreting once you’ve reached adult age.
False. GH is secreted throughout life.
***It peaks at puberty and lessens as you get older.
If there is decreased secretion of GHRH (due to hypothalamic dysfunction), then there is decreased GH secretion. This leads to failure to generate __________ (i.e., IGF-1). GH or _________ resistance can occur because of a deficiency of receptors for them (due to their underproduction).
Somatomedins
Somatomedin
GH excess is mostly due to a GH-secreting pituitary _________. Consequences depend on the development stage, before puberty results in _________ and after puberty results in _________.
Adenoma
Gigantism
Acromegaly
To diagnose acromegaly, we first need to test the IGF-1 levels. We don’t measure GH because it fluctuates so much throughout the day, but IGF-1 remains constant. If it is elevated then there is a chance of acromegaly. Second, we need to do the _______ _______ _______ test. Normally, if there is a lot of blood glucose then this will make GH levels drop. So, with the test the patient drinks a very sugary drink and their GH levels are measured at various times after drinking it. If the GH levels stay high and don’t drop like they’re expected to, then the patient has acromegaly.
Oral Glucose Tolerance
What are the 3 requirements to diagnose a patient with acromegaly?
1) Increased serum IGF-1
2) Failure to suppress serum GH (via oral glucose tolerance test)
3) Pituitary enlargement on MRI
What is unique about the release of Prolactin?
Rather than being stimulated to be released, it is in constant inhibition of being released. So, in order to secrete the inhibition has to be inhibited!
Prolactin is synthesized by Lactotropes (Mammotropes). Secretion begins to increase by the 5th week of pregnancy, and is pulsatile. Prolactin is under tonic inhibition by hypothalamic __________.
Dopamine
Primary function of Prolactin is to stimulate and maintain _________. It also suppresses _________ (inhibits LH and FSH), causing decreased reproductive function and suppressed sexual drive.
Lactation
GnRH
Describe the PRL axis and its feedback mechanisms.
Hypothalamus produces dopamine and TRH. TRH stimulates the release of Prolactin from the anterior pituitary, which goes to the breasts to stimulate lactation. Dopamine inhibits the release of Prolactin from the anterior pituitary.
Prolactin signals to the hypothalamus to produce more Dopamine to further inhibit its own secretion. Also signals to the hypothalamus to inhibit GnRH secretion, resulting in the loss of secretion of FSH and LH from the anterior pituitary.
Hormone-producing pituitary ________ release an active hormone in excessive amounts into the bloodstream. The patients usually experience symptoms related to the hormone action on the body. Examples include Prolactinoma (overproduction of Prolactin), Acromegaly/Gigantism (overproduction of GH), and Cushing’s Disease (overproduction of ACTH).
Adenoma
This is the result of hormone being UNDER produced within the pituitary.
Hypopituitarism
***Causes include brain damage, pituitary tumors, non-pituitary tumors, infections, infarction, autoimmune disorders, pituitary hypoplasia or aplasia, or genetic disorders.
The posterior pituitary secretes…
Oxytocin (from SON)
ADH (from PVN)
Oxytocin starts out as ___________ and is cleaved into _________ in the hypothalamus. It then moves down the Hypothalamic-hypophyseal tract (axons of neurons) and is stored as Oxytocin in the posterior pituitary. A carrier protein called ________ is with it, keeping it from secreting out into the blood stream. This protein is cleaved and Oxytocin is released to go its targets, the breasts and uterus.
Prepro-oxyphysin
Pro-oxyphysin
Neurophysin
What are the actions of Oxytocin?
Milk letdown – major stimulus is suckling
Uterine contraction – stimulated by dilation of cervix or orgasm
