1. Chapter 6, The Endocrine Hypothalamus

2. 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

3. 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

4. Hypothalamus – chemical messengers

5. Hypothalamus

6.  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 eminence Median eminence links to anterior pituitary via hypophysial portal system  In humans - ~2.5cm long, ~4g in weight

7. SON and PVN comprise magnocellular system Parvocellular system

8. 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?

9. 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

10. Hypothalamus-pituitary association & feedback

11. 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.

12. 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)

13. 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

14. 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

15. 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

16. 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?

17. 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

18. 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

19. 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.

20. 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

21. 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

22. 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