Chapter 6, The Endocrine Hypothalamus

Small bit about the pituitary

Pituitary thought to be the “master gland” Integral in a variety of responses Remove it and see atrophy of these responses

However studies of removal and re-implantation (at other locations) do not support level of importance

Studies that block pituitary-hypothalamic association demonstrate importance of hypothalamus Additional lesion studies reinforce this importance

Hypothalamus is going to act as a ‘go-between’ for incorporating neural inputs and hormone responses

General information on hypothalamus Hypothalamus a cluster of nerve nuclei

Groupings of neurons Neurosecretory cells

Secrete both inhibitory and stimulatory hormones Hypothalamic hormone products are all protein hormones Receptors in anterior pituitary all G-protein coupled

cAMP levels will be up-regulated, actions activated Prime target tissue (but not only) – the pituitary

Anterior and posterior pituitary differ a bit (more in future chapters)

Receptors for hypothalamic hormones can exist outside the pituitary Gonadotropin releasing hormone (GnRH) receptors on ovary

Hypothalamus – chemical messengers

Hypothalamus

Hypothalamus

Hypothalamus basal part of the diencephalon lying below the thalamus Forms walls and floor of third ventricle Includes optic chiasma, tuber cinereum, infundibulum, and mammillary bodies

Lower part of tuber cinereum is the median eminenceMedian eminence links to anterior pituitary via

hypophysial portal system In humans - ~2.5cm long, ~4g in weight

SON and PVN comprise magnocellular system

Parvocellular system

Control of hypothalamic function

Hypothalamus regulated by internal hormonal signals & neural inputs from other sources (many cases outside of organism) Final common pathway for signals to reach pituitary

Involved in non-endocrine functions Food intake, (this has impact on GH secretion, but indirectly)

Feedback mechanisms in conjunction with pituitary Short-, long-loops, auto-feedback

Rhythmic secretion of hormones and activity Circadian rhythms, suprachiasmatic nuclei = clock?

Feedback loops

Short and long loop feedback systems mostly defined by how many steps involved

Autoinhibition is a way for endocrine tissues to fine-tune their production

Hypothalamus-pituitary association & feedback

Alternate view

Need to start thinking in layers.

Keep in mind long-loop, short-loop, and auto-inhibition are happening simultaneously.

It is not a system with particular order and no one aspect of feedback trumps any other.

Hypothalamic hormones

Some of the major hypothalamic hormones (there are more!) Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GnRH) Gonadotropin-inhibiting hormone (GnIH) Growth hormone releasing hormone (GHRH) Growth hormone release-inhibiting hormone (AKA

Somatostatin) Prolactin releasing hormone (PRH) Prolactin releasing-inhibiting hormone (AKA Dopamine) Thyrotropin-releasing hormone (TRH) MSH release-inhibiting hormone (Also Dopamine)

Thyrotropin-releasing hormone (TRH)

Will induce thyroid stimulating hormone (TSH) and prolactin release from pituitary

Produced in paraventricular nuclei & preoptic area Small active hormone

Larger pro-TRH molecule yields several TRHs Notable in that it has no free N-terminal amino group

TRH found in many other species Ultimately this hormone is going to initiate a path of response

that activates the thyroid gland, this is an important structure Conservation among species

Somatostatin (SST)

Inhibits growth hormone (GH) release from the anterior pituitary AKA: Growth hormone release-inhibiting hormone Also inhibits thyroid stimulating hormone (TSH) secretion

Produced in anterior periventricular region Also secreted from CNS, gut, and pancreas

Inhibits glucagon, gastrin, insulin, & secretin

Growth hormone releasing hormone (GHRH)

Now also termed somatocrinin Induces growth hormone release from the anterior

pituitary Similar sequences to several gut peptides

Produced from arcuate nuclei & ventromedia nuclei Long half-life of 50 min. Variable release over multiple time scales Ghrelin – also induces GH release, and influences

hunger Important to note the linking between hormones that

influence hunger and one that influences growth

Gonadotropin-releasing hormone (GnRH)

Induces follicle stimulating hormone (FSH) and luteinizing hormone (LH) release from anterior pituitary Release is pulsatile and this is important to what hormone is

induced Produced from preoptic area and suprachiasmatic

nucleus Receptors in tissues other than brain, use in rest of body

also unclear Found on ovary in some animals

Local regulation of estrogen production perhaps Found in the uterus of mammals

Set up for response during pregnancy? Local regulation of tissue responses in preparation for pregnancy?

Gonadotropin-releasing hormone (GnRH)

15 different varieties have been described vertebrates Genes for variants

on multiple chromosomes

Sequence highly conserved

Most spp. have 2+ types, uses unclear

Gonadotropin-inhibiting hormone (GnIH)

Newer hypothalamic hormone – first described 2000 Mammalian version also called RFamide-related

peptide-3 (RFRP-3) Produced by the paraventricular nuclei Inhibits luteinizing hormone (LH) release, unclear

about follicle stimulating hormone (FSH) Works with GnRH to control pulsatile LH release

GnIH secreting neurons found outside hypothalamus, may influence other neural and physiological processes

GnIH release influenced by stress, developmental state, and photoperiod

Corticotropin-releasing hormone (CRH)

Induces adrenocorticotropic hormone (ACTH) and β-endorphin release from the anterior pituitary

From parvocellular region of paraventricular nuclei 41 amino acids

Highly conserved across species, again, may not want to mess up the response generated here

Long half life – 60 min.

Dopamine

Dopamine found in hypophysial portal system Released from arcuate nuclei Remember it can also be a neurotransmitter

Acts as a prolactin-release-inhibiting factor (PIF) Prolactin may be continually released unless inhibited Experiments in vitro show dopamine inhibits

Dopamine also appears to function as melanotropin-release inhibitory factor Not clear of the use of this in humans

Prolactin-releasing hormone

Questionable as to what this hormone is TRH, vasoactive intestinal polypeptide (VIP), or oxytocin all candidates

Orphan receptor identified as PRH receptor Evidence that whatever it is it’s coming from the paraventricular nuclei

Nursing can induce prolactin release, but the physical act may be a block on dopamine production

Prolactin is an old hormone with extensive exaptation, control of it may be complex due to this

Hypothalamic disorders

Tumors, trauma, infections, congenital deformations, genetic defects, & vascular alterations Can affect secretion selectively or collectively Usually leads to decreased pituitary function

Deficits in individual hormones Hypothalamic hypothyroidism – TRH deficient Olfactory-genital dysplasia – GnRH deficient

Kallmann’s Syndrome