Principles of Neuroendocrinology
Transcript of Principles of Neuroendocrinology
![Page 1: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/1.jpg)
Principles of Neuroendocrinology
• Anatomy of the hypothalamic-pituitary axis• Neurohumoral secretion• Brain as endocrine organ and target• Endocrine servomechanisms• Chronobiology and endocrinology• Stress• Hormone pulsatility
![Page 2: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/2.jpg)
![Page 3: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/3.jpg)
![Page 4: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/4.jpg)
Hypothalamic-Hypophyseal Circulation
• Anterior pituitary: fed by plexus of portal veins which drain median eminence of the hypothalamus.
• Portal circulation contains high concentration of hypothalamic hormones
![Page 5: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/5.jpg)
Developmental Biology of the Pituitary
![Page 6: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/6.jpg)
Anatomy of Hormone-Producing Cells in the Anterior Pituitary Gland
![Page 7: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/7.jpg)
Hypothalamic Hormones-1• Gonadotropin releasing
hormone (GnRH, LHRH)
• Thyrotropin releasing hormone (TRH)
• Corticotropin releasing hormone (CRH)
Stimulates LH and FSH release
Stimulates TSH release (also prolactin)
Stimulates ACTH release
![Page 8: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/8.jpg)
Hypothalamic Hormones-2• Growth hormone
releasing hormone (GHRH)
• Somatostatin (SRIH)
• Dopamine
Stimulates GH release
Inhibits release of GH and TSH
Inhibits release of prolactin
![Page 9: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/9.jpg)
Brain as a Target Organ• Testosterone may be metabolized to
– Androgen: dihydrotestosterone (DHT)– Estrogen: estradiol
• Estrogen may be metabolized to– Estrogenic steroid: estriol– Catecholestrogen: ?activity
• Neurosteroids– Steroid hormones can interact with cell surface receptors
(progesterone metabolites and GABA receptors)
![Page 10: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/10.jpg)
Endocrine Servomechanisms• Homeostatic feedback
loops:– Hormone A regulates
secretion of hormone B
• Closed feedback:– Hormone B also regulates
hormone A
• Negative feedback loops– Long, short, “ultashort”
• Positive feedback loops
![Page 11: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/11.jpg)
Neuroendocrine Feedback Loops
![Page 12: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/12.jpg)
Chronobiology
• Rhythms may reflect passive adjustment to the environment (exogenous rhythm) or may originate from within the organism itself (endogenous rhythm; e.g., circadian rhythms).
• Rhythms may or may not be sleep-entrained.• Effectiveness of feedback mechanisms may vary
with periodicity.• Disturbances of rhythms may result in dis-ease
![Page 13: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/13.jpg)
![Page 14: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/14.jpg)
![Page 15: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/15.jpg)
![Page 16: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/16.jpg)
![Page 17: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/17.jpg)
![Page 18: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/18.jpg)
Adrenarche Adrenopause
![Page 19: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/19.jpg)
![Page 20: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/20.jpg)
Cyclical Cushing Syndrome
Urin
ary
corti
sol/c
reat
inin
e ra
tio
![Page 21: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/21.jpg)
Cyclical Cushings JCEM 2004
![Page 22: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/22.jpg)
![Page 23: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/23.jpg)
![Page 24: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/24.jpg)
![Page 25: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/25.jpg)
![Page 26: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/26.jpg)
![Page 27: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/27.jpg)
![Page 28: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/28.jpg)
![Page 29: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/29.jpg)
JCEM 83: 1827 - 1834, 1998
Acute and Prolonged Critical Illness as Different Neuroendocrine Paradigms
![Page 30: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/30.jpg)
Stress overcomes the effects of negative feedback and over-rules the circadian
oscillator
![Page 31: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/31.jpg)
![Page 32: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/32.jpg)
![Page 33: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/33.jpg)
![Page 34: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/34.jpg)
![Page 35: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/35.jpg)
Pituitary Hormones are Released in a Pulsatile Fashion• Pulsatile secretion may reflect underlying
neuronal rhythms• Time to synthesize and store new
hormones• Internalization of peptide/receptor• Avoid spill-over of CNS neurohormones
into general circulation
![Page 36: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/36.jpg)
Kallmann Syndrome
• Hypogonadotropic hypogonadism– failure to enter or progress through puberty– low serum LH, FSH, and testosterone
suggesting defect in hypothalamic GnRH• Anosmia• Midline defects, including cleft palate• Misc. neurologic abnormalities
![Page 37: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/37.jpg)
![Page 38: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/38.jpg)
Knobil’s Experiment to Replace GnRH in Rhesus Monkey
• Remove endogenous GnRH by ablating medial basal hypothalamus
• GnRH replacement therapy– Hourly bolus (physiologic rhythm)– Continuous infusion
![Page 39: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/39.jpg)
![Page 40: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/40.jpg)
![Page 41: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/41.jpg)
Knobil Experiment with GnRH Replacement Therapy
• Physiologic pulsatile GnRH infusion stimulates hormone secretion from gonadotroph
• Continuous (nonphysiologic) infusion inhibits gonadotroph
![Page 42: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/42.jpg)
Sine qua non for pulsatility: the hormone must have a
relatively short half-life compared to the interval
between injections or secretion of hormone
![Page 43: Principles of Neuroendocrinology](https://reader030.fdocuments.in/reader030/viewer/2022012410/616a5d6111a7b741a351b2be/html5/thumbnails/43.jpg)
GnRH Agonist Therapy: Chemical Castration
• Hormone-sensitive tumors– Prostate cancer– Uterine fibroids (leiomyomata)
• Menstrual cycle related diseases– Endometriosis– Catamenial syndromes
• Preparation for in vitro fertilization• Precocious puberty