Hypothalamus and Pituitary: Neuroendocrinology, Circadian Rhythms

Lecture 2

neuroendocrinology

link between nervous and endocrine systems

nervous: driving force, quick response

endocrine: responds to nervous system signals, sustained response, restoration of homeostasis

1 cell can have both

hypothalamus

major controller of neuroendocrine function

integration center between brain, autonomic nervous system, endocrine glands

needed for appropriate responses to environmental factors

maintenance of homeostasis

coordination of physiological functions and behaviors (reproduction, feeding, emotional, stress responses, temperature

anterior pituitary

adenohypophysis

posterior pituitary

neurohypophysis

extension of hypothalamus

hypothalamic-anterior pituitary hormones

hypothalamus: dopamine (prolactin-inhibiting hormone)

pituitary: prolactin

target/function: mammary gland (milk); lactation

no prolactin-stimulating hypothalamic hormone

default state of prolactin is repression

needs to be de-repressed to lactate

feed-forward and feedback regulation example

hypothalamic-pituitary-adrenal (HPA) axis

feed forward

drive from hypothalamus to pituitary to target

hypothalamic hormone- drives pituitary hormone

pituitary hormone- drive target (adrenal) hormone

negative feedback

input to hypothalamus and pituitary about the concentrations of a peripheral hormone

inc target hormone- dec hypothalamic and pituitary hormone (receptor occupancy is high, inhibits hip/pit output)

dec target hormone- inc hypothalamic and pituitary hormones (receptor occupancy is low, stimulates hip/pit output)

adenoma

benign tumor of epithelial cell origin

common but most are non or sub functional

symptoms: expanding intracranial mass (headache, diabetes insipidus, vision changes) or to hormone excess/deficiency

etiology pituitary adenoma

any pituitary cell type can undergo hyperplasia

pathophys pituitary adonoma

arise from clonal expansion (1 cell multiplies)

genetic causes, especially MEN-1 (multiple endocrine neoplasia-1)

prolactinoma

most common anterior pituitary disorder

most are asymptomatic

can be associated with galactorrhea

symptoms: menstrual disturbances, infertility, loss of libido

decreased bone density

treatment: surgery, dopamine agonists

dopamine

inhibitory to pituitary PRL release, so pharmacologic dopamine agonists can inhibit PRL made by the prolactinoma

panhypopituitarism

complete loss of all pituitary hormones

hypopituitarism

loss of one or more pituitary hormone

etiology of hypopituitarism

sudden onset: trauma, infarction, hemorrhage, pituitary stalk section

pathophys hypopituitarism

low conc of pituitary hormones together with low conc of target hormones

clinical manifestations hypopituitarism

dependent upon extent and duration of insufficiency

sometimes can be compensated (ex: vasopressin deficiency is treated by inc water intake)

cell bodies

2 regions in hypothalamus: paraventricular nucleus (PVN) and supraoptic nucleus (SON)

vasopressin and oxytocin neurons

large neurons

project through pituitary stalk and into posterior pituitary

nerve terminals in posterior pituitary

full of large secretory vesicles that store vasopressin or oxytocin

from stimulus, vesicles are released directly into systemic circulation

vasopressin

aka anti-diuretic hormone and arginine vasopressin

hypothalamic “osmostat”- osmoreceptors

urine conc inc

inc blood osmolality

triggers thirst

release vasopressin

water conservation

enhances water retention in collecting ducts of kidney

oxytocin

stimulates uterine smooth muscle contraction during childbirth

during lactation

oxytocin is responsible for reflexive milk ejection during suckling

within the brain

oxytocin is important to behaviors including maternal behavior and pair bonding in monogamous species

vasopressin and oxytocin

9 amino acid peptides that are structurally similar

hypothalamic cell bodies that synthesize them are large and are magnocellular neurons

receptors are GPCR

oxytocin receptor

on breast tissue, pituitary, brain, uterus, arterioles

vasopressin receptors

3 types

V1a, V1b or V3, V2

diabetes insipidus

AVP-deficiency (central)

AVP-resistant (nephrogenic)

clinical presentation diabetes insipidus

polyuria (increased water intake) that persists even under conditions of dehydrations, 20 L/day

thirst

nocturne (adults) and bed wetting (kids)

avp deficiency (central)

loss of avp from trauma, intracranial tumor, surgery

can be treated by increasing water intake, pharmacotherapy (desmopressin)

nephrogenic avp resistance (nephrogenic)

kidneys loss of ability to respond to circulating vasopressin by retaining water

due to defect in vasopressin receptor or water channel on renal collecting ducts

sometimes induced by drugs

treated by low salt diet and drinking enough water to avoid dehydration

sometimes treated with diuretics

clinical presentation syndrome of inappropriate vasopressin (ADH) secretion (SIADH)

hyponatremia without edema

associated with confusion, lethargy, weakness, seizures, coma

etiology syndrome of inappropriate vasopressin (ADH) secretion (SIADH)

vasopressin-secreting tumors (non-hypothalamic or pituitary), CNS disorders, pulmonary disorders, drugs

other disorders can be associated with SIADH (adrenal insufficiency, hypothyroidism)

pathophys syndrome of inappropriate vasopressin (ADH) secretion (SIADH)

not well understood

involves serum Na imbalance through water intake, renal solute delivery, and VP-mediated distal renal tubular water retention

management syndrome of inappropriate vasopressin (ADH) secretion (SIADH)

restriction of fluid and water intake

removal of a tumor

vasopressin antagonists are available but not used unless CHF or extreme cases

hypothalamus

suprachiasmatic nucleus- SCN (neural control) of circadian rhythms

pineal gland

melatonin (hormonal control) of circadian rhythms

cycles

hourly- hormone pulses

daily- circadian/diurnal

weekly/monthly- estrous/menstrual

yearly- seasonal

pineal gland and melatonin

tiny, pinecone shaped endocrine gland

secretes melatonin

melatonin

tryptophan metabolite

hormone of darkness

highest secretion at night

roles of melatonin

sleep aid

inhibits reproductive activity (puberty, seasonal breeding)

seasonality

antioxidant

immune regulation

aging

learning, memory, cognition

disorders of circadian system are associated with increased

sleep disturbances, sleep apnea

obesity

type 2 diabetes mellitus

cancers- hormonally associated

cognitive dysfunction

alzheimer’s disease

neuropsychiatric disorders

circadian disruption fromj

jetlag, shift work, dim light at night can inc risk for disorders of the the circadian system