Lecture 1: Reproductive Endocrinology Flashcards
What are steroid hormone base, their main classes, plasma half life, and binding
- Molecules derived from cholesterol (lipid soluble). 3 hexagons+ 1 pentagon
- Cholesterol-> (rate limiting step regulated by LH) ->Prostagens (and corticosteroids)-> androgens-> oestrogens
- long plasma half life
- bind to intracellular receptor, goes to the nucleus and alters gene expression
Describe the transport of steroid hormones- progestagens, androgens and oestrogens
1-2% free hormone
Albumin carries majority Oestrogens, minority androgens: this is high capacity, low affinity carrier so more are likely to be bioavailable
Progestagens are split nearly equally between cortisol binding globulin and albumin
Sex hormone binding globulin carries majority Androgens, minority Oestrogens: this high affinity low capacity transport so less bioavailable
What are the principle actions of Androgens, what is the most potent form and where is it made (2’ pathway too)
Supports spermatogenesis, induce and maintain differentiation of male tissues, promote protein anabolism, somatic growth and ossification.
Most potent is 5alphaDHT. this is made from via local 5a reductase acting on circulating Testosterone (made from testis).
2’ pathway is through circulating androstenedione in extraglandular tissues.
What are the principle actions of Oestrogens, what is the most potent form and where is it made (2’ pathway too)
Stimulates secondary sex characteristics of females, growth and activity of mammary gland, proliferative phase of endometrium, and calcification
Most potent is Estradiol. this is made from granulosa cells of growing follicle in reproductive, non pregnant women.
2’ pathway is in adipose tissue through androstenedione-> testosterone-> oestrone (mostly post menopausal women and males
What are the principle actions of Prostagens, what is the most potent form and where is it made (2’ pathway too)
Stimulates the growth of mamillary glands but suppresses secretion of milk, inhibits cervical mucus secretion: making a plug, general mild catabolic effect raising basal body temperature for implantation and pregnancy
Most potent is Progesterone- made from corpus luteum in post ovulatory phase of menstrual cycle (and in placenta). Otherwise small amount circulating from adrenal cortex.
What is the function of hypothalamus
Integrates sensory information (light, odour, sound) carried by nervous system and converts it into hormonal information for homeostatic regulation of reproduction, stress, body temperature etc VIA pulsatile release of hormones
What is the function and tissue composition of the anterior pituitary gland
Produces hormones which are secreted according to hypothalamus control.
Has a mix of cell types which respond to specific stimuli and release specific hormones into systemic circulation.
What is the function and tissue composition of the posterior pituitary gland
Stores hormones that were made in the hypothalamus.
Made of glial tissue and axonal termini
Compare the connection between the hypothalamus and anterior pituitary vs posterior pituitary leading to release of products and the final products released by both
Anterior: connected via hypophyseal portal system
Neurosecretory neurons make … releasing/…. inhibiting hormone eg. Gonadotrophin releasing hormone,
in the cell body, which travel to axonal terminus in vesicles.
In response to nerve impulses these hormones are secreted into hypophyseal portal system to trigger different types secretory cell groups to release of ant pituitary hormones: eg. LH, FSH
Also Growth hormone releasing hormone leads to Growth hormone release.
Posterior: connected via direct magnocellular neurons.
Neurosecretory neurons make neurosecretory peptide hormones Oxytocin and Vasopressin (ADH) which travel down to posterior pit and stored in the axon terminals as secretory vesicles and released when nerve impulses travel down the same nerve, triggering exocytosis into systemic circulation.
What is the role of oxytocin and vasopressin
Oxytocin is for SM contraction: milk ejection and uterine contraction during childbirth. Secretion triggered by nipple stim or cervical distension
Vasopressin: Anti diuretic hormone: acts on the kidney to retain water and causes vasoconstriction (elevates bp)
Describe the hypothalamus- pituitary- gonadal axis for males and females - 3 steps
- Hypothalamus->GnRH-> Anterior pituitary.
- GnRH acts on gonadotrophs in ant pit which releases into systemic circulation to bind on receptors in the testis or ovary
a) FSH: growth of ovarian follicles or spermatozoa (spermatogenesis)
b) LH: secretion of female sex hormone and stimulation of ovulation. OR stim of testosterone production
3) Estradiol and Testosterone has negative feedbacks to ant pituitary and hypothalamus products.
Inhibin feeds back to Ant pituitary in both genders - against FSH only.
(also progesterone feeds back to hypothalamus in females)
What is the pattern of GnRH release by hypothalamus and how is it regulated? What is the therapeutic application
GnRH has pulsatile secretion every 60-90minutes. This is to prevent receptor desensitisation and down regulation and leads to pituitary hormones to have pulsatile release too
The pulse interval and amplitude is regulated by
- estradiol, neural influences (puberty), brain opioids, gonadotrophins themselves.
Therapeutically if synthetic GnRH is given continuously via infusion over long periods, there will be an initial period of oversecretion of FSH and LH then downregulation/desensitiation - less recycling of receptors. This helps to lower the level of steroid hormone which is good for Endometriosis, b cancer, precocious puberty, BprostaticH, IVF therapy .
Describe the Growth hormone pathway including feedback and the disease associated with dysregulation of this pathway + treatment
- Hypothalamus -> GHRH -> Ant Pit somatotrophs
- Ant pit releases Growth hormone which works on liver to make IGF-1 which promotes cell growth in wide range of tissues
- IGF-1 has inhib feedback to Ant Pit and promotes somatostatin at the hypothalamus which works against GH.
Disease: Acromegaly- excessive GH and IGF-1 resulting in gradually enlarged facial features, hand, feet. Arising from GH or GHRH secreting tumour and treated via somatostatins, GH receptor antagonists, surgical removal of tumour
Describe the Thyroid hormone pathway including feedback and the disease associated with dysregulation of this pathway + treatment
- Hypothalamus -> TRH -> Ant Pit thyrotrophs
- Ant pit releases Thyroid Stimulating hormone (and prolactin) which works on thyroid gland to make T3 and T4 involve in regulating the rate of metabolism
- T3 and T4 has inhib feedback to Ant Pit and hypothalamus and promotes somatostatin at the hypothalamus which inhibits TSH release
What is hashimotos thyroiditis, thyroid hyperplasia and Graves disease and their treatments
Hashimoto’s thyroiditis: autoimmune disease where thyroid is damaged so there is high TSH but low T4 production. Treated with Thyroid hormone pills
Graves disease: Hyperthyroidism: overproduction of T4, enhancing negative feedback and therefore reducing TSH. Treated with radioactive iodine to reduce thyroid size and methimazole: reduce T4 production
Thyroid hyperplasia: Iodine deficiency prevents thyroid from making T3 and T4. this reduces negative feedback resulting in higher TRH and TSH levels and eventual thyroid hyperplasia. Treated by giving iodine
