Neuroendocrinology and autonomic functions Flashcards
What functions is the hypothalamus involved in the control?
sleep–wakefulness, thermoregulation, feeding, metabolic energy expenditure, drinking and fluid homeostasis, growth and reproduction.
What is the structure of the hypothalamus?
consists of many nuclei clustered around the third ventricle. At its anterior end the floor of the ventricle thickens to become the median eminence which projects as the infundibulum (part of the pituitary stalk) to the posterior pituitary gland. The hypothalamus is divided into three longitudinal zones—the innermost of which, the periventricular zone, surrounds the third ventricle—and four subdivisions along its rostro-caudal axis.
What input does the hypothalamus get from the hippocampus?
● By way of the subiculum, part of the hippocampal formation, which projects via the fornix to the mammillary bodies
●By way of the septum, also via the fornix, to connect with all three zones of the hypothalamus
How does the hypothalamus get input from the amygdala?
via the stria terminalis, a loop that follows a similar course to the fornix, and the amygdalofugal pathway.
What is the pathway of hypothalamic output via mammillary bodies?
via the mammillothalamic tract goes to the anterior thalamic nuclei (ATN) that are connected to the cingulate cortex. The cingulate cortex projects back to the hippocampal formation, so closing a loop (hypothalamus–ATN–CC–hippocampus–hypothalamus) termed the Papez circuit.
What larger network is the papez circuit a part of?
includes the septum, amygdala, and prefrontal cortex which is concerned with emotion and memory.
What connections of the mammillary bodies are implicated in memory?
It’s reciprocal connections via the mammillotegmental tract with the ventral tegmental nuclei in the midbrain
The medial forebrain bundle passes through the lateral hypothalamic zone. What does it consist of?
monoaminergic axons ascending from brainstem nuclei. Many noradrenergic and serotonergic, but not dopaminergic, axons synapse with hypothalamic neurons.
What input to the hypothalamus is important for hypothalamic control of the ANS?
The paraventricular hypothalamus and the lateral hypothalamic area receive visceral sensory input from the nucleus of the solitary tract (NST)
The pituitary gland is divided into the neurohypophysis and the adenohypophysis. What is the structure of the neurohypophysis?
It is a direct outgrowth of the hypothalamus, consists of the posterior lobe, the median eminence, and the infundibulum.
What is the structure of the adenohypophysis?
consists of the anterior lobe, an intermediate lobe (poorly developed in humans), and the pars tuberalis (an extension surrounding the infundibulum). The pars tuberalis and the infundibulum together make up the pituitary stalk
What are the two groups of peptide-secreting neuroendocrine cells in the para ventricular nuclei of the HT?
Magnocellular and parvocellular cells
Where do magnocellular cells send axons?
through the median eminence down the infundibular stalk into the posterior lobe as the tuberohypophyseal tract.
Where are hormones made and released from magnocellular cells?
made in the cell bodies of the magnocellular cells and transported down their axons for release in the posterior lobe.
What do parvocellular cells terminate on?
They have short axons which terminate on capillaries in the median eminence. These capillaries drain into long portal vessels that descend to form venous sinusoids in the anterior lobe; this vascular bed is the portal system.
What happens to hormones secreted by parvocellular cells?
Hormones secreted by the parvocellular neurons into the median eminence are carried via the hypothalamic-pituitary portal circulation to the anterior lobe.
How are homones delivered to the body from the pituitary gland?
Both lobes have fenestrated capillaries that lie on the blood side of the blood–brain barrier that drain into the systemic circulation
What hormones do magnocellular cells in the supraoptic (SON) and paraventricular (PVN) nuclei secrete?
the nonapeptides arginine vasopressin and oxytocin.
What is AVP, also known as antidiuretic hormone (ADH) secreted in response to?
an increase in extracellular fluid osmolality or reduced blood volume.
What is the effect of ADH?
increases the water permeability of nephron collecting ducts, thereby promoting water reabsorption. This reduces extracellular fluid osmolality and urine output (an antidiuretic effect) so restoring blood volume. Thus, AVP acts as a negative feedback regulator, defending set points in body fluid osmolality and blood volume.
Where are the osmoreceptors which respond to changes in osmolality?
vascular organ of the lamina terminalis (OVLT), one of the
circumventricular organs of the brain which lie on the blood side of the blood–brain
barrier. Osmolality-sensitive neurons in the OVLT synapse with the PVN and SON cells and increase their firing rate as osmolality rises.
hypovolemia greater than 10% stimulates AVP secretion, what is the role of baroceptors in this?
Hypovolemia lowers mean arterial blood pressure. This is detected by stretch recep-
tors (baroreceptors) in the walls of the carotid sinus and aorta. The afferents of these pressure sensors run in the glossopharyngeal (IX) and vagus (X) cranial nerves to the nucleus of the solitary tract (NST) in the medulla. The NST activates noradrenergic neurons in the ventrolateral medulla which project to the PVN and SON to bring about AVP release. A reduced blood pressure causes decreased firing of the baroreceptor afferents and hence disinhibition of the circuitry triggering AVP secretion.
What is renin secreted by?
the juxtaglomerular apparatus (JGA) of the kidney in response to several factors contingent on a fall in blood volume.
What is renin and what is its function?
Renin is a proteolytic enzyme which cleaves a plasma protein, angiotensinogen, to yield a decapeptide, angiotensin I. This is further cleaved by angiotensin converting enzyme (ACE), expressed on pulmonary endothelial cells, to the octapeptide, angiotensin II
What are the effects of angiotensin II?
Angiotensin II stimulates the subfornical organ (a circumventricular organ), neurons of which stimulate AVP secretion. In addition, AII stimulates drinking, vasoconstriction, and
the secretion of aldosterone; all actions which help restore blood volume and pressure.
what aspects of reproductive function is oxytocin implicated in ?
Its stimulation of smooth muscle contraction underlies the milk ejection reflex in lactating females, and
maintenance of uterine contractions during parturition
Suckling is the most potent stimulation for milk ejection, What is the pathway of this reflex?
Primary afferents from the areolar and nipple skin relay with spinothalamic tract neurons in the dorsal horn of the spinal cord. Spinothalamic input causes oxytocin secretion via an undefined neural pathway
from midbrain to the PVN and SON.
How does the uterine smooth muscle become sensitive to oxytocin at term?
a rise in maternal estradiol/ progesterone ratio upregulates oxytocin receptors in uterine smooth muscle
What evokes the secretion of oxytocin during labour?
pressure of the fetal head on the cervix, via a reflex pathway similar to that for milk ejection.
What is the effect of oxytocin during birth?
oxytocin stimulates contractions of the uterine smooth muscle, further increasing the pressure of the fetus on the cervix.
This positive feedback mechanism is the Ferguson reflex.
What social interactions does oxytocin facilitate?
● Pair bonding—the tendency of two individuals in a sexual relationship to stay together—in both sexes
● Triggering maternal behavior
● Trust between individuals
What mediates the social interactions facilitated by oxytocin?
mediated by projections of hypothalamic oxytocin
neurons to limbic structures involved in emotion, and to the ventral tegmental area
(VTA) of the dopaminergic reward system.
What mechanism underlies pair bonding?
Oxytocin neurons fire during sexual intercourse in both women and men, and oxytocin produces feelings of pleasure and increased libido.It is postulated that oxytocin release becomes
conditioned by repeated intercourse with the same partner. In this model sexual/romantic love is seen as an addiction to a specific individual organized by oxytocin.
What is the mechanism of oxytocin triggering maternal behaviour?
rats involves increased oxytocin signaling to the VTA and consequently increased dopamine release from the nucleus accumbens.
How does oxytocin facilitate trust?
oxytocin could operate by
suppressing fear circuitry of the amygdala and brainstem.
What is the mechanism of the feelings of love and empathy felt by individuals dosed with 3,4-methylenedioxy-
methamphetamine?
could be because MDMA stimulates oxytocin secretion by activation of 5-HT1A serotonin receptors.
How does acute stress inhibit oxytocin release?
via actions of noradrenaline (norepinephrine) and
adrenaline (epinephrine).
What are the two types of hypophysiotropic hormones?
those that excite secretion are termed releasing hormones, those that inhibit are called release-inhibiting hormones.
Secretion from the neuroendocrine axes is modulated by negative feedback, what is this?
defined as a mechanism that acts to hold some variable at a set point. In endocrinology the set point is generally the blood concentration of a hormone and the negative feedback operates at several levels of the neuroendocrine axis.
What occurs in the neuroendocrine axis when the concentration of the end product hormone exceeds the set point?
more receptors are activated in the hypothalamus and anterior pituitary which consequently reduce their output of hormones. The effect is that, after some delay, the concentration of end product hormone falls
What happens in the neuroendocrine axis when the concentration of the hormone falls below the set point?
the hypothalamus and pituitary secrete more of their hypophysiotropic and trophic hormones, provoking an increase in concentration of the end product hormone.
What is autofeedback inhibition?
special case of negative feedback in which a substance directly inhibits its own synthesis
What is the pattern of secretion of hypothalamic hormones?
pulsatile with a period of 60–180 min. This drives pulsatile release of anterior pituitary hormones. The amplitude and period of the pulses varies on a circadian (about a day) basis and in some instances on longer time scales.
What is the function of the HPA axis?
regulates the synthesis and secretion of glucocorticoids, a group of steroid hormones which influence energy substrate metabolism. Most NB- cortisol
In the HPA axis what do cells in the paraventricular nucleus of the hypothalamus secrete?
corticotrophin releasing hormone (CRH), a peptide which acts synergistically with arginine vasopressin to stimulate release of adrenocorticotrophic hormone (ACTH) from corticotrophs
What is ACTH cleaved from?
large precursor, pro-opiomelanocortin.
Where does negative feedback of cortisol operate?
at the hippocampus, hypothalamus and pituitary
Where is the brain biological clock that drives the circadian rhythm?
Suprachiasmatic nucleus
How is ACTH/ cortisol secretion affected by the circadian rhythm?
ACTH pulses are greatest early in the morning and decline through the day to reach a low point around midnight. Cortisol secretion follows a similar pattern. This daily rhythm is influenced by the timing of light and dark, sleep and meals.
Which two receptors mediate the effects of cortisol?
mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These are members of a nuclear receptor superfamily that includes receptors for other steroids and for thyroid hormones.
When cortisol receptors are unbound, where are they situated?
present in the cytoplasm, complexed with heat shock proteins, molecular chaperones that stabilize the receptors into their functional configuration.
What is the effect of glucocorticoids/ cortisol on the receptor?
Glucocorticoids such as cortisol diffuse readily across cell membranes. Binding of cortisol causes the receptor to translocate into the nucleus where it binds to specific sequences of DNA, hormone responsive elements, thereby increasing or decreasing the transcription of specific genes
What is the distribution of mineralcorticoid and glucocorticoid receptors?
Mineralocorticoid receptors are in greatest numbers in limbic structures. Glucocorticoid receptors are more widespread, and expressed in glia as well as neurons. corticotrophs of the anterior pituitary, CRH- secreting neurons of the hypothalamus, and hippocampal neurons express GRs
Why does cortisol affect different target tissues depending on its concentration?
MRs have a high cortisol affinity they are mostly occupied at basal concentrations of the steroid. By contrast, GRs have a low affinity so are only occupied when the cortisol concentration is high, such as early morning.
The hypothalamic–pituitary–adrenal axis is activated in stress. What is the definition of stress?
generally it is a state seen in situations that derange homeostasis, or in which there is actual or perceived harm, loss, or challenge. Stressors, agents that cause stress, can be physiological or psychosocial, often arising in situations over which an individual has little control. An operational definition of stress is any state in which there is a large and/or prolonged rise in ACTH and glucocorticoid concentrations.
Why is cortisol useful in acute stress?
overall effect is to harness long-term energy substrates and convert them to readily available substrates, glycogen and glucose. In addition, cortisol potentiates the effects of catecholamines.
