HLC Tutorial

1. HLC Tutorial

2. CONTENTS Review of the ovaries and menstrual cycle - Dr Davinia White Disordered Ovarian Function, anovulation and infertility - Dr Davinia White Case Histories: Endocrine causes of anovulation and their management - Dr Davinia White The Menopause, pros and cons of HRT - Dr Davinia White Clinical aspects of the endometrium - Professor Jenny Higham The cervix in gynaecology practice - Professor Jenny Higham The cervix in labour - Professor Jenny Higham Birth - Professor Jenny Higham Fetal growth rates - Lorin Lakasing Intra-uterine growth restriction - Lorin Lakasing Genito-urinary development - Dr Jenifer Loudon Cardiac development and changes in circulatory system at birth - Dr Jenifer Loudon + video supplementary slides: Development of the genital system [pdf] - Dr Mark Hill Normal growth in childhood, measuring children - Dr Nicola Bridges Abnormalities of growth - Dr Nicola Bridges Obesity - Dr Nicola Bridges Growth charts and case studies - Dr Nicola Bridges

3. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

4. oestradiol & progesterone produced by granulosa cells from antral follicles >9.5mmoestradiol & progesterone produced by granulosa cells from antral follicles >9.5mm

5. Females born with lifetime’s supply of oocytes Follicles may remain quiescent at this stage for up to 1/2 a century. Through the influence of a rise in follicle stimulating hormone (FSH) during the first days of the cycle, a few ovarian follicles are stimulated.[17] These follicles, which were present at birth[17] and have been developing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will stop growing, while one dominant follicle in the ovary will continue to maturity. The follicle that reaches maturity is called a tertiary, or Graafian, follicle, and it forms the ovum.[17] As they mature, the follicles secrete increasing amounts of estradiol, an estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. Follicles may remain quiescent at this stage for up to 1/2 a century. Through the influence of a rise in follicle stimulating hormone (FSH) during the first days of the cycle, a few ovarian follicles are stimulated.[17] These follicles, which were present at birth[17] and have been developing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will stop growing, while one dominant follicle in the ovary will continue to maturity. The follicle that reaches maturity is called a tertiary, or Graafian, follicle, and it forms the ovum.[17] As they mature, the follicles secrete increasing amounts of estradiol, an estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium.

6. Talk through menstrual cycle Talk through menstrual cycle

7. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

8. Definitions Normal menstrual cycle: Cycle length 21-35 days with no more than a 4 day variation between cycles Amenorrhoea : Absence of menses >6 months Primary : no previous periods in a women of 16 years + eg. Congenital disorders of the ovary and genital tract Secondary: at least one previous spontaneous period More common Oligomenorrhoea : Cycle >42 days Anovulation : Absence of ovulation , ? 25% infertilitym most causes treatable

9. Hyperprolactinaemia High prolactin (normal = 50-500 mU/l – here in 1000’s) High Prolactin ? Low Dopamine ?Inhibits GnRH ? Decreased FSH & LH ? Amenorrhea Cause: 50% = Pituitary adenomas Symptoms: Common cause of amenorrhoea (Secondary) + galactorrhea + visual problems Treatment: Dopamine agonists Bromocriptine / Cabergoline Dopamine agonists normalise prolactin Dopamine agonists normalise prolactin

10. HMG human menopausal gonadotrophin hMG gonadotrophins LH and FSH extracted from urine, purified and reconstituted for daily IM injection various degrees of purity with hMG standard ampoule 75 IU FSH, LH dose varies from 75IU to <1IU high purity, additional steps to remove urinary proteins now available as recombinant FSH and LH, therefore no urinary contaminants HMG human menopausal gonadotrophin hMG gonadotrophins LH and FSH extracted from urine, purified and reconstituted for daily IM injection various degrees of purity with hMG standard ampoule 75 IU FSH, LH dose varies from 75IU to <1IU high purity, additional steps to remove urinary proteins now available as recombinant FSH and LH, therefore no urinary contaminants

11. Polycystic ovary syndrome Characterised by: Anovulatory menses / amenorrhoea Androgen excess clinical (hirsutism/acne/frontal hair loss) Polycystic ovaries (USS) Metabolic syndrome eg. central obesity, insulin resistance

12. Treatment: Clomiphene citrate= Hypothalmic anti-oestrogen ? FSH + LH secretion. Increased weight = Less likely to respond Fail to conceive after > 9 cycles of clomiphene ? Maybe resistant ALTERNATIVE hMG Ovarian diathermy Diathermy to 4 points on each ovary Trauma makes ovaries more responsive to endogenous gonadotrophin secretion Polycystic ovary syndrome Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either through the release of excessive luteinizing hormone (LH) by the anterior pituitary gland or through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus. The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These "cysts" are actually immature follicles, not cysts ("polyfollicular ovary syndrome" would have been a more accurate name). The follicles have developed from primordial follicles, but the development has stopped ("arrested") at an early antral stage due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a 'string of pearls' on ultrasound examination. The condition was first described in 1935 by Dr. Stein and Dr. Leventhal, hence its original name of Stein-Leventhal syndrome. A majority of patients with PCOS have insulin resistance and/or are obese. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. PCOS is characterized by a complex set of symptoms, and the cause cannot be determined for all patients. In many cases it is characterised by a complex positive feedback loop of insulin resistance and hyperandrogensim. In most cases it can not be determined which (if any) of those two should be regarded causative. Experimental treatment with either antiandrogens or insulin sensitizing agents improves both hyperandrogenism and insulin resistance. PCOS is also likely to have a genetic predisposition, and further research into this possibility is taking place. A few specific genetic defects are known accounting only for a small fraction of cases, the rest may be due to the combination of several factors. Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese patients creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and estrogens (which inhibits FSH via negative feedback).[18] Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS. Insulin resistance is a common finding among patients of normal weight as well as those overweight patients. PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.[19][20] Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either through the release of excessive luteinizing hormone (LH) by the anterior pituitary gland or through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus. The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These "cysts" are actually immature follicles, not cysts ("polyfollicular ovary syndrome" would have been a more accurate name). The follicles have developed from primordial follicles, but the development has stopped ("arrested") at an early antral stage due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a 'string of pearls' on ultrasound examination. The condition was first described in 1935 by Dr. Stein and Dr. Leventhal, hence its original name of Stein-Leventhal syndrome. A majority of patients with PCOS have insulin resistance and/or are obese. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. PCOS is characterized by a complex set of symptoms, and the cause cannot be determined for all patients. In many cases it is characterised by a complex positive feedback loop of insulin resistance and hyperandrogensim. In most cases it can not be determined which (if any) of those two should be regarded causative. Experimental treatment with either antiandrogens or insulin sensitizing agents improves both hyperandrogenism and insulin resistance. PCOS is also likely to have a genetic predisposition, and further research into this possibility is taking place. A few specific genetic defects are known accounting only for a small fraction of cases, the rest may be due to the combination of several factors. Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese patients creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and estrogens (which inhibits FSH via negative feedback).[18] Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS. Insulin resistance is a common finding among patients of normal weight as well as those overweight patients. PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.[19][20]

14. Many other endocrine disorders (eg Cushing’s, acromegaly) are rare causes of menstrual dysfunction but commonly present with menstrual abnormalities Endocrine disorders associated with ovulatory dysfunction Hypothalamic-pituitary disease GnRH deficiency isolated or identified cause prolactinoma acromegaly Cushing’s non-functioning tumours Sheehan’s syndrome Adrenal disease CAH, virilising tumours, Addison’s disease Thyroid disease hypothyroidism hyperthyroidism

15. Ovarian Hyperstimulation Syndrome As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hyperpermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process through the production of hCG.As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hyperpermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process through the production of hCG.

16. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

17. Menopause SUMMARISE HORMONAL CHANGES !SUMMARISE HORMONAL CHANGES !

18. The hypothalamic-pituitary-ovarian axis

19. The hypothalamic-pituitary-ovarian axis in the perimenopause As ovarian reserve of follicles declines, oestradiol levels fall and FSH increases High FSH may “hyperstimulate” the next “crop” of follicles Multiple antral follicles and/or follicular cysts may develop Oestradiol levels may transiently become supraphysiological and FSH is suppressed Abnormal menstrual patterns are common As ovarian reserve of follicles declines, oestradiol levels fall and FSH increases High FSH may “hyperstimulate” the next “crop” of follicles Multiple antral follicles and/or follicular cysts may develop Oestradiol levels may transiently become supraphysiological and FSH is suppressed Abnormal menstrual patterns are common

20. The hypothalamic-pituitary-ovarian axis in the post-menopause Androgen production decreases but still produced by adrenal and, in small amounts, by ovary Low levels of oestrogen in circulation produced mainly by peripheral conversion of androgen Gonadotrophins remain high Androgen production decreases but still produced by adrenal and, in small amounts, by ovary Low levels of oestrogen in circulation produced mainly by peripheral conversion of androgen Gonadotrophins remain high

21. Menopause SUMMARISE HORMONAL CHANGES !SUMMARISE HORMONAL CHANGES !

22. Oestrogen deficiency Vasomotor: Sweat / palpatations/ headaches Genitourinary tract: Vaginal dryness / urge incontinence, dysuria, urinary frequency Neurological/ Psychological: Forgetfulness/ depression/ loss of libido/ tiredness Skeletal: Osteopenia/osteoporosis Cardiovascular: Risk of CHD and stroke Part if at risk of osteoporosis / severe vasomotor sx Part if at risk of osteoporosis / severe vasomotor sx

23. Choice of HRT Oestrogen alone (only if uterus has been removed) Oral (conjugated equine oestrogens or oestradiol valerate) Vaginal Creams Transdermal (patches; gel) Intranasal Implant Oestrogen/progestagen combination Cyclical or continuous progestagen orally Intrauterine progestagen Selective (o)estrogen receptor modulators (SERMS)

24. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

25. Endometrial cancer Postmenopausal women over 50 with postmenopausal bleeding (10%) Majority adenocarcinomas Increased risk with infrequent ovulation and obesity Menorrhagia Excessively heavy and regular [“ovulatory”] period Common ! Often find nothing Often associated with anemia (IDA) Endometriosis Endometrium outside the uterine lining eg. Pelvis Debilitating symptoms of : Painful periods [dysmenorrhoea] Pain with intercourse [dyspareunia] Infertility Treatments suppression with drugs or surgery

26. Imaging and sampling the endometrium Ultrasound Cheap, quick and relatively non-invasive Endometrial thickness (depends on stage of cycle) and structure of uterus In postmenopausal women, thickness should not exceed 5 mm Endometrial biopsies Irregular bleeding/ thickened endometrium/ cancer? Often hysteroscopy also- biopsy alone may miss pathology Hysteroscopy - Diagnostic Direct image of the whole endometrial cavity Usually the investigation of choice for persistent irregular / abnormal bleeding Allows directed biopsy of abnormal areas Magnifies & allows visualisation of interior Can be performed as an outpatient using especially designed fine instruments Most accurate imaging method (not 100%)

27. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

28. The normal cervix SCJ or transformation zone (TZ) – meeting of squamous vaginal epithelium with glanduar lining of cervical os Dynamic changes of TZ with age / hormones Puberty – scj MOVES down Post menopause moves up The epithelium of the cervix is varied. The ectocervix (more distal, by the vagina) is composed of nonkeratinized stratified squamous epithelium. The endocervix (more proximal, within the uterus) is composed of simple columnar epithelium.[1] The area adjacent to the border of the endocervix and ectocervix is known as the transformation zone. The Transformation zone undergoes metaplasia numerous times during normal life. When the endocervix is exposed to the harsh acidic environment of the vagina it undergoes metaplasia to squamous epithelium which is better suited to the vaginal environment. Similarly when the ectocervix enters the less harsh uterine area it undergoes metaplasia to become columnar epithelium. Times in life when this metaplasia of the transformation zone occurs: puberty; when the endocervix everts (moves out) of the uterus with the changes of the cervix associated with the normal menstrual cycle post-menopause; the uterus shrinks moving the transformation zone upwards All these changes are normal and the occurrence is said to be physiological. Puberty – scj MOVES down Post menopause moves up The epithelium of the cervix is varied. The ectocervix (more distal, by the vagina) is composed of nonkeratinized stratified squamous epithelium. The endocervix (more proximal, within the uterus) is composed of simple columnar epithelium.[1] The area adjacent to the border of the endocervix and ectocervix is known as the transformation zone. The Transformation zone undergoes metaplasia numerous times during normal life. When the endocervix is exposed to the harsh acidic environment of the vagina it undergoes metaplasia to squamous epithelium which is better suited to the vaginal environment. Similarly when the ectocervix enters the less harsh uterine area it undergoes metaplasia to become columnar epithelium. Times in life when this metaplasia of the transformation zone occurs: puberty; when the endocervix everts (moves out) of the uterus with the changes of the cervix associated with the normal menstrual cycle post-menopause; the uterus shrinks moving the transformation zone upwards All these changes are normal and the occurrence is said to be physiological.

29. How to do a smear? Visualise cervix with Cuscoe’s speculum ? Rotate spatula or brush through 360° focus on squamo-columnar junction (SCJ) Spatulas / Brush Smear on glass slide immediately New – Liquid Based Cytology [LBC] – wash away debris Fix with 95% ethyl alcohol or aerosol alternative, stain with H&E Smears: sensitivity improved by LBC MAY SEE: Nabothian follicle” or mucus retention cyst LOOKING FOR Cervical intraepithelial neoplasia (CIN)

30. Epithelial changes in CIN Premalignant & treatable CIN1 = dysplastic changes involving one third of squamous epithelium CIN2 = lower two thirds involved CIN3 = entire depth involved. Basement membrane not breached Dyskaryosis of the uterine cervix is a condition in which some of the epithelial cells near the external os show abnormalities in their cellular nuclei.Premalignant & treatable CIN1 = dysplastic changes involving one third of squamous epithelium CIN2 = lower two thirds involved CIN3 = entire depth involved. Basement membrane not breached Dyskaryosis of the uterine cervix is a condition in which some of the epithelial cells near the external os show abnormalities in their cellular nuclei.

32. The abnormal smear DYSKARYOSIS (cytology) MILD MODERATE SEVERE CIN1 CIN2 CIN3 DYSPLASIA (histology) CYTO = cells / histology = tissues CYTO = cells / histology = tissues

33. Treatment CIN 1 - ?observe & repeat colposcopy CIN 2 & 3 - excision TZ by Using electrical current or laser Approx. 35% CIN3 progress to invasive disease over 10 years Invasive carcinoma: squamous or adeno- Examination under anaesthetic to decide stage / spread If early can remove surgically +/- radiotherapy or chemotherapy

34. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

35. Labour = “the onset of regular uterine contractions accompanied by the progressive effacement and dilatation of the cervix” First stage 16+ hours From the onset of regular contractions and associated dilatation and effacement of the cervix until full dilatation [10cm]

36. Cervical Changes DURING LABOUR CERVIX TRANSFORMS ! Long firm approx. 3 cm long cylinder ?Thin/ flat structure = “effacement” ? DILATATION Prostaglandins inhibit collagen synthesis and encourage collagen breakdown

37. Labour = “the onset of regular uterine contractions accompanied by the progressive effacement and dilatation of the cervix” First stage 16+ hours From the onset of regular contractions and associated dilatation and effacement of the cervix until full dilatation [10cm] Second stage 30 mins – 2 hours, active pushing for 1 hour From full cervical dilatation to delivery of the baby Contractions of uterine muscle, accompanied by “retraction” or shortening Later by the maternal effort of pushing Third stage 10 – 30 mins Delivery of the placenta and membranes Blood loss is 300ml

38. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

40. Decompensated = increased afterload ie. hyperTDecompensated = increased afterload ie. hyperT

43. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

44. Fetal development

45. Three layer embryo (week 3)

46. Goes wrong ? Spinal Bifida

47. Genitourinary DevelopmentCardiovascular  Development

48. 1) 4th week of development, the primordial gut is closed at both the cranial and caudal ends by the oropharyngeal and cloacal membranes (Clocoal membrane= becomes anal / genital membreanes (in animals persists ). 2) During the period of rapid growth of the midgut, there is a normal herniation of bowel into the proximal portion of the umbilical cord. (Midgut = embryolgical origin of intestine) 3) The urorectal septum separates the urinary tract from the rectum- becomes more pronounces and moves towards caudal – bottom ! What we see here is that the 1) 4th week of development, the primordial gut is closed at both the cranial and caudal ends by the oropharyngeal and cloacal membranes (Clocoal membrane= becomes anal / genital membreanes (in animals persists ). 2) During the period of rapid growth of the midgut, there is a normal herniation of bowel into the proximal portion of the umbilical cord. (Midgut = embryolgical origin of intestine) 3) The urorectal septum separates the urinary tract from the rectum- becomes more pronounces and moves towards caudal – bottom ! What we see here is that the

49. urachus is a fibrous remnant of the allantois, a canal that drains the urinary bladder of the fetus that joins and runs within the umbilical cord As the the rectum moves down the kidneys begin to develop = called mesonephros ! urachus is a fibrous remnant of the allantois, a canal that drains the urinary bladder of the fetus that joins and runs within the umbilical cord As the the rectum moves down the kidneys begin to develop = called mesonephros !

50. Pronephros = 1st stage of kidney (all signs disappeared by 4 weeks) ? Mesonephros = intermediae kidney ? ,etonephros ? final Pronephros = 1st stage of kidney (all signs disappeared by 4 weeks) ? Mesonephros = intermediae kidney ? ,etonephros ? final

53. Didelphus and variates

54. External genitalia Ambiguous until 12 weeks Labioscrotal swellings Urogenital folds The gonads are undifferentiated until week 5 They develop in the genital ridges in the coelomic epithelium Primordial germ cells migrate from the yolk sac Both testis and ovaries are abdominal until 28 weeks when the testis begins to descend through the inguinal canal The gonads are undifferentiated until week 5 They develop in the genital ridges in the coelomic epithelium Primordial germ cells migrate from the yolk sac Both testis and ovaries are abdominal until 28 weeks when the testis begins to descend through the inguinal canal

55. Failure of the labioscrotal folds to fuse will lead to hypospadias in the male ypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus (the opening, or male external urethral orifice). ..Failure of the labioscrotal folds to fuse will lead to hypospadias in the male ypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus (the opening, or male external urethral orifice). ..

56. Genitourinary DevelopmentCardiovascular  Development

57. Two Dorsal Aortae Two ventral Aortae Linked by the aortic arches Aortic Arches

58. Aortic Arches

59. Folding

60. From the front

61. From the front

62. Heart- key structures

63. http://www.indiana.edu/~anat550/cvanim/ Good animations

64. Lisa Webber 2008 Menstrual cycleInfertility Menopause EndometriumCervix BirthFetal Growth Embryology Growth

65. 65 Normal growth is a marker of health and nutrition Plot charts to make sure its okay!

66. 66

67. Commonest concern about growth is short stature Most people presenting with short stature are normal Genetic (short parents) / medical or nutrition problems in the neonatal period or infancy/ low birth weight/ short patents Boys with pubertal delay

68. Growth hormone deficiency: Diagnosis with stimulation test, treat with recombinant GH daily injections t/o childhood Turners Syndrome: 45XO Karyotype Short stature with normal growth hormone Ovarian failure resulting in failure to progress in puberty Many girls with this have characteristic features- webbed neck, wide carrying angle of arms, hypoplastic nails

70. leptin Hormone secreted by fat with receptors in the hypothalamus Increased fat mass correlates with increased leptin concentrations Humans have been identified with both leptin deficiency and leptin receptor mutations Ghlerin produced by stomach in response to hunger ? Increased food intake NPY- neuropeptide y / Agouti-related peptide (AgRP) neurone ? Increased appatite Leptin (White adipose tissue mainly) ? Inhibits NPY/ Agouti-related peptide (AgRP) neurone ? Decreased app Proopiomelanocortin/ Cocaine- and amphetamine-regulated transcript, neuropeptides ? Inhibits food intake leptin Hormone secreted by fat with receptors in the hypothalamus Increased fat mass correlates with increased leptin concentrations Humans have been identified with both leptin deficiency and leptin receptor mutations Ghlerin produced by stomach in response to hunger ? Increased food intake NPY- neuropeptide y / Agouti-related peptide (AgRP) neurone ? Increased appatite Leptin (White adipose tissue mainly) ? Inhibits NPY/ Agouti-related peptide (AgRP) neurone ? Decreased app Proopiomelanocortin/ Cocaine- and amphetamine-regulated transcript, neuropeptides ? Inhibits food intake

72. Buy membership! Najia Sultan ns806@ic.ac.uk