PH1124 - Reproductive hormones 2 Flashcards
what is the role of progesterone on the body?
- stimulate gene expression and so cell growth in tissues that express the PR
what are the effects of progesterone on the body? (3)
- contribution to breast development
- maintain uterus structure; control secretory changes in uterus (endometrium) in preparation for and to maintain pregnancy
- causes rise in basal body temperature (after ovulation in luteal phase when progesterone is highest)
what is progesterone clinically used to treat? (2)
- combined with oestradiol as part of HRT
- IVF (to supplement body’s natural progesterone to aid pregnancy)
what are the side effects of clinically using progesterone?
- a very slightly increased risk of breast cancer with certain HRT strategies
what is the general mechanism for reproductive hormones?
- hormone enters cells and binds to specific hormone receptor
- receptor conformation change, dimerization and translocation of this hormone receptor complex to the nucleus
- DNA binding of hormone receptor complex to its specific ‘Hormone Response Element’ (HRE is a short sequence of DNA in the promoter of target genes that can bind the specific ligand-bound hormone receptor)
- influences transcriptional activity of certain genes so there is gene expression (or repression)
- encoded protein synthesis & impact on target cell growth
what regulates gonadal steroidogenesis?
- the endocrine function of the gonads to synthesise reproductive hormones is carefully regulated by the Hypothalamic-Pituitary-Gonadal axis (HPG axis)
where is the HPG axis?
- hypothalamus is a small structure at the base of the forebrain
what does the HPX axis link?
- links the nervous system to the endocrine system via the pituitary gland that is also in the brain
what is the hypothalamus composed of? (3)
- composed of 11 zones or ‘nuclei’
- each is able to secrete several different hormones (which are produced from neurons)
- these are secreted directly into the bloodstream to easily reach and regulate the pituitary gland as there is no effective BBB (blood brain barrier)
what processes does the hypothalamus indirectly control? (2)
- hypothalamic nuclei have indirect control of different body processes eg. hunger, body temperature, mood, sleep, thirst etc
- also controls reproductive hormone secretion from the gonads
what does the hypothalamus release? (2)
- releases gonadotrophin releasing hormone (GnRH=LHRH) from ventromedial neurons
- act via the bloodstream (hypophyseal portal system) on the nearby anterior pituitary gland
how does GnHR release gonadotrophins? (3)
- GnRH acts on GnRH receptors found on pituitary ‘gonadotrope’ cells
- activates intracellular enzymes in the pituitary gonadotropes
- enzymes trigger synthesis of gonadotrophins
what is the anterior pituitary able to synthesise?
- anterior pituitary contains the specialised cells (gonadotropes) that are able to synthesise both gonadotrophins FSH & LH in response to GnRH
what does LH or FSH production depend on?
- depends on pulsatile GnRH; FSH and LH is released into the bloodstream & comprises the endocrine stimulation for the gonads
what is the gonadotrophin mechanism of action on the gonads? (3)
- gonadotrophins = LH and FSH
- LH and FSH each bind to different GPCR-type transmembrane receptors expressed on cells within ovary and testes
- this then activates GPCR signalling, and thereby gonad function
what are the main functions of LH? (2)
- in females they act on ovarian follicles and helps induce ovulation
- in males they act on testes leydig cells so they can produce testosterone (which in turn is important for spermatogenesis)
what are the main functions of FSH? (2)
- in female they promote ovarian follicle development and oestrogen production from granulosa cells
- in males they stimulate spermatogenesis in testes by acting on the sertoli cells
what is the direct negative feedback mechanism for reproductive hormone synthesis?
- steroid hormones (testosterone/oestrogen) directly feedback onto anterior pituitary to decrease secretion of gonadotrophins FSH/LH
what is the indirect negative feedback mechanism for reproductive hormone synthesis?
- steroid hormones inhibit their own production indirectly by inhibiting hypothalamus production of GnRH
what are other negative regulators of gonadal steroidogenesis?
- inhibin
what is inhibin and what does it do? (3)
- a protein hormone that is additional negative regulator of FSH
- in females inhibin is released by the ovary granulosa cells in response to either FSH stimulation or oestrogens
- in males inhibin is released by the testes sertoli cells in response to either FSH stimulation or androgens
what is the positive feedback of the HPG axis? (2)
- occurs during the follicular phase of the menstrual cycle where high oestrogen levels induce further LH production
- this leads to further increases in the reproductive hormone level to trigger ovulation
what are the other hormones that are secreted from pituitary gland contribute to reproductive biology? (2)
- oxytocin
- prolactin
what is oxytocin and what is it secreted by? (2)
- an important peptide hormone for childbirth that stimulates uterine motility (during labor) & breast milk production
- produced by the hypothalamic neurons and transported down axons then stored in and subsequently secreted by the posterior pituitary
when is oxytocin secreted? (2)
- secreted in response to increasing oestrogens by labour contractions and by breast feeding
- positive feedback as oxytocin induces contractions during labor which in turn promotes further oxytocin release to further progress labor to delivery
what is prolactin? (2)
- peptide hormone secreted by anterior pituitary lactotropes in response to elevated oestrogens (during ovulation or pregnancy)
- classed as a further gonadotrophin because it influences reproductive organs and breast
what are the main functions of prolactin?
- in breast it stimulates lactation and also maternal behaviour
- provides further negative feedback of oestrogen production
what is the negative feedback mechanism for prolactin?
- during lactation prolactin suppresses GnRH release from the hypothalamus which decreases LH, FSH
- thereby oestrogens (disrupting return of menstrual cycle so it may result in lactational amenorrhea)
what is gametogenesis?
- formation of female or male gametes
what are mature gametes called? (2)
- ovum (egg)
- spermatozoa (sperm cells)
what is gametogenesis call in females and males? (5)
- females oogenesis process
- males spermatogenesis process
- gametogenesis occurs in the gonads (ovary or testis)
- ova produced from ‘germ cells’ called oogonium/primary oocyte
- sperm produced from ‘germ cells’ called spermatogonium
what is spermatogenesis and what does it start with? (2)
- formation of mature male gametes (the sperm cells) in testes within seminiferous tubules
- starts with precursor (germ or stem) cells called spermatagonia
what happens in the seminiferous tubules? (3)
- spermatagonia (germ cells) undergo mitosis to give diploid primary spermatocytes
- spermatocytes then undergo meiosis to give haploid spermatides
- they then differentiate into sperm (spermatozoa)
where is the location of spermatogenesis
seminiferous tubules
why are leydig cells and sertoli cells in the seminiferous tubules important for spermatozoa development?
- they create the physical & chemical environment that favours spermatogenesis
- they secrete hormones & further essential factors to regulate spermatogenesis
what are the hormones secreted to aid spermatozoa development? (3)
- testosterone (from leydig cells only)
- androgen binding protein (ABP) (from sertoli cells only)
- inhibin (from sertoli cells only)
what are leydig cells?
- interstitial cells (pale with crystals) adjacent to seminiferous tubules in the testes
what are leydig cells stimulated by?
- they are stimulated by pituitary-derived gonadotrophin LH (LH is driven by fast GnRH pulses, so non-cyclical input)
what is the function of leydig cells? (3)
LH acts via LH receptors on the leydig cells
- the LH drives testosterone production from androstenedione by the leydig cells
- testosterone is needed at high levels for spermatogenesis
where do the sertoli cells extend from and to?
- sertoli cells are ‘nurse’ cells extending from basement membrane of tubule to lumen
what is the function of sertoli cells? (3)
- provide structural, nutrient and metabolic support required for developing sperm
- secrete substances initiating the meiosis (eg growth factors)
- guide sperm to lumen via their junctions
what are sertoli cells stimulated by?
- stimulated by testosterone from leydig ells
- simulated by pituitary-derived FSH as they express FSH receptors
what do sertoli cells secrete?
- androgen binding protein (ABP)
- secrete inhibin in response to FSH or testosterone
what does ABP serecreted by sertoli cells do?
- the ABP binds testosterone from Leydig cells to ensure testosterone is at a high enough concentration in seminiferous tubule lumens to allow spermatogenesis
what does inhibin serecreted by sertoli cells do? (2)
- inhibin negatively feedsback onto pituitary to inhibit FSH
- inhibin thus acts to negatively regulate spermatogenesis
