BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/28/2012, 1st hour Page1 Clicker Q In what part of the cell would you find the receptors for peptide hormones? - Plasma membrane - Water soluble, cannot get into cell unless it binds to a receptor on the cell surface Review Chemical structure of hormones - Protein/peptides - Steroids - Tyrosine derivatives amines - Sherwood’s Tables 4-4 and 18-2 Summary tables Negative feedback - Hormones negatively feedback on the two primary organs that will stimulate their own secretion - Prohibit any further secretion of their own secretion Positive feedback - Rare - Estrogen will stimulate more of its own secretion Adenylyl cyclase-cAMP system - Signaling system, use of surface receptor and second messenger systems - Cell membrane phospholipid system - G protein mediated Lecture 3 Pineal Gland, Pituitary Gland Reading assignment: Sherwood p. 678 (8th ed) and p. 684 (7th ed) Target cell responsiveness - After hormones are secreted, target cells have to respond to the hormones - Hormones cannot have any effect if the target cell does not respond - Mechanisms to enhance or inhibit hormone function that are found from target cell responsiveness o Down regulation of the hormone receptor Once peptide hormone binds receptor, the hormone receptor complex is internalized, receptor is no longer on cell surface, cannot respond to any more hormone Desensitizing cell to specific hormone o Hormone permissiveness When a hormone binds its receptor, it will have an effect on target cell, but it does not a full effect Requires action of another hormone – one hormone must be present for the full effect of another hormone on that cell When the other hormone is present, then the main hormone’s full effect will occur Example: Thyroid hormone increases the number of epinephrine (EPI) receptors on EPI target cells Enhance effects of main target hormone of that cell o Hormone synergism 2 or more hormones act on a target cell, can be the same hormone (multiple hormone binding) Combined effect is greater than each one binding separately BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/28/2012, 1st hour Page2 Hormone A bind singly, when 2 A hormones bind, they have more than 2x the effect o Hormone antagonism Opposite of synergism 1 hormone inhibits the effect of another hormone (by causing the loss of another hormones receptors) and decreases its effectiveness Adenylyl cyclase system, have Gs (stimulatory) and Gi (inhibitory) Different receptors for the two different G protein, basically cancel out effect of each other During pregnancy, progesterone inhibits responsiveness of uterus to estrogen Example diagram: - Down regulation o Hormone binds receptor, becomes internalized, no longer on surface, cannot bind any further hormone - Synergism o Multiple hormones binding, result in the combined effect to be much greater on the target cell Pineal Gland - Secretes the hormone melatonin o Helps regulate circadian rhythm of body o Light/dark cycle - Specialized photoreceptor cells in retina that bind to light signals, relay those signals to the SCN (found in hypothalamus, above the optic chiasm) - SCN = suprachiasmatic nucleus - When light stimulates SCN, signals go to pineal gland to inhibit melatonin secretion o Not secreted during light hours o Primarily secreted at night, during loss of light - These photoreceptors are not our typical rods and cones o About 1-2% of retinal ganglion cells have this function o Use protein melanopsin as the receptor Pineal gland and SCN - SCN is a collection of neurons functioning as the Master Biological Clock as the pacemaker for the circadian rhythm - Maintain a light/dark cycle BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/28/2012, 1st hour Page3 SCN and circadian rhythm - Upregulation of clock proteins during dusk and dawn, in low light hours, o Get a peak production of these clock proteins in cytoplasm of the SCN of the cells (neurons) at night - Synthesized in the cytoplasm - As they start to increase in number in the cytoplasm, these proteins eventually migrate back into the nucleus - In the nucleus these clock proteins become transcription inhibitors - Gene is inhibited for the clock protein, inhibit their own gene transcription - Half-life of 6-12 hours, degrade and get into nucleus, inhibit their own production - Between dusk and dawn, in the middle of the night, peak production of clock protein o In the morning, slowly decline clock protein o At noon, lowest levels of clock protein (degradation of protein in the nucleus) o In the evening, clock protein levels begin to rise (loss of inhibition of gene transcription) o Repeat cycle - Play role in jet lag, clock proteins have their own 24 -25 hour cycle - Keep process up over 25 hour cycle - Light helps reset that clock to get into a new cycle - Travelling in different time zones, body gets readjusted to a new clock protein cycle Synchronization of circadian rhythms - Clock protein cycle continues without activation of light - Light stimulates the SCN, activate retinal ganglion cells, inhibits pineal gland from melatonin secretion - During daylight, low melatonin during - In the dark, get inhibition of retinal ganglion cells, no activation of SCN, pineal gland is active, produce melatonin during dark hours - Start increasing synthesis in afternoon, high levels of clock protein will inhibit the SCN at peak, pineal gland is active in secreting melatonin - Clock protein is high at night when we have elevated melatonin - Clock proteins are inhibiting the SCN from inhibiting pineal gland - @ night, Highest levels of clock protein = high melatonin production BHS 116.2 – Physiology Notetaker: Vivien Yip - - Date: 11/28/2012, 1st hour Page4 Primary function of SCN is to inhibit pineal gland o When there are high amounts of clock protein, this inhibition is lost o Pineal gland can then secrete melatonin Don’t know exact function of clock proteins Overview: During night hours, high levels of clock protein, lack of SCN activation, lack of retinal ganglion cell activation, lack of inhibition of pineal gland secrete melatonin Other roles for melatonin - Induces sleep o Sleep supplements are primarily melatonin - Inhibit hormones that stimulate reproduction - Use for birth control aid (method of birth control) o At high levels, inhibits ovulation - Animals trigger for seasonal breeding o Migration, hibernation in some species - Antioxidant o Slow down aging process Anatomy of the pituitary gland - “Master gland” - secretes a lot of hormones that control other hormones in the body - Sits in the sella turcica with a surrounding sinus - Connected to the hypothalamus via the hypophysial stalk - 2 different origins of anterior (adenohypophysis) and posterior (neurohypophysis) pituitary o Both have very different functions and cell types - Middle region of pituitary gland: pars intermedia o Considered part of the adenohypophysis o Avascular o More important in lower vertebrates o Secretes melanocyte stimulating hormone (MSH) o Utilize melanin to change skin color and avoid predation o Stimulates melanin producing cells to produce more melanin o Ex. Chameleons o Humans, not such a big role Anterior Pituitary - Ectodermal origin, from Rathke’s pouch, an invagination of pharyngeal epithelium - Cells appear epithelial - Hormones have major roles in metabolic function - 5 different anterior pituitary cell types produces 6 prominent hormones and 1 lesser hormone (melanocyte stimulating hormone, MSH) - All protein/peptide hormones o All water soluble hormones, no carrier required for transportation Types of anterior pituitary cells: Acidophils (red stain) - Somatotropes or alpha cells o Produce growth hormone o Make up 30-40% of the anterior pituitary cells, most prominent - Lactotropes or E cells BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/28/2012, 1st hour Page5 o produce prolactin Basophils (blue stain) - Corticotropes or beta cells o produce ACTH, adrenocorticotropic hormones and MSH (melanocyte stimulating hormone) o make up about 20% of anterior pituitary cells o second most prominent - Gonadotropes or epsilon cells o Produce (FSH) follicle stimulating hormone and (LH) luteinizing hormone Chromophobes (no stain) - Poorly staining basophils - Thyrotropes or gamma cells o Produce TSH thyroid stimulating hormone Can now stain with labelled antibodies to give specific cell types - Stained with an antibody specific for human growth hormone - This orange stain identifies what cell type? o Somatotropes (GH) Growth Hormone - Promotes growth through protein synthesis, cell division and differentiation (ACTH) Adrenocorticotrophic Hormone - Plays a big role in glucose metabolize - Controls glucose, protein and fat metabolism - Promotes growth of the adrenal cortex (TSH) Thyroid stimulating Hormone - Main job is to stimulate secretion of thyroid hormone from thyroid gland - Promotes growth of the thyroid gland - Controls the rate of secretion of thyroid hormones, thyroxine T4 and triiodothyronine which control the rates of most intracellular chemical reactions in the body Prolactin - Promotes mammary gland development and milk production (FSH) Follicle Stimulating Hormone AND (LH) Luteinizing Hormone - Control growth of ovaries and testes and their hormonal production Summary - 5 main cell types - 1 minor - 5 of the 6 are tropic - Tropic hormones: o Regulate secretion of hormone by another endocrine organ o Stimulate/maintain structural integrity of that endocrine organ - ACTH stimulate adrenal gland to produce cortisol but also maintains integrity of that gland - GH stimulates growth of tissues of all parts of the body - Prolactin is the only non tropic hormone produced by anterior pituitary hormone o Does not stimulate another organ to secrete another other hormone Clicker Q Where would you find the clock proteins? - SCN BHS 116.2 – Physiology Notetaker: Vivien Yip Date: 11/28/2012, 1st hour Page6 Hormone Summary chart – Anterior Pituitary Gland Hormone GH ACTH TSH Prolactin (only NON tropic) LH, FSH Function Promotes growth through protein synthesis, cell division and differentiation Controls glucose, protein and fat metabolism Promotes growth of the adrenal cortex Stimulate secretion of thyroid hormone from thyroid gland Promotes growth of the thyroid gland Controls the rate of secretion of thyroid hormones, thyroxine T4 and triiodothyronine which control the rates of most intracellular chemical reactions in the body Secreting cells Somatotropes Stain Red, acidophile Corticotropes Blue, basophils Thyrotropes No stain, chromophobe Promotes mammary gland development and milk production Control growth of ovaries and testes and their hormonal production Lactotrope Red, acidophile Gonadotrope Blue, basophils