Flashcards in Ovary and follicular development/Puberty Deck (72):
What are the functions of ovarian follicles?
maintenance of viable oocyte, produce steroid hormones essential for prep of repro tracts for fertilization, implantation and pregnancy, postovulatory differentiation to CL providing P during luteal pahse and 1st trimester
What do granulosa cells synthesize?
estrogens- estradiol-17B (E2) and estrone (E1); Inhibin A and B, Follistatin, Activin, growth factors and cytokines
What do theca cells synthesize?
progesterone, 20a-hydroxyprogesterone, androstenedione, testosterone, inhibin A and growth factors
What do luteal cells synthesize?
progesterone, E2 (early part), inhibin A and growth factors
What does FSH regulate?
synthesis and secretion of estrogen
What does LH regulate?
synthesis and secretion of progesterone and androgen
How do theca cells synthesize androstenedione and testosterone? Where does it go?
take in LDL turn to cholesteryl-ester, esterase to cholesterol, StAR and PBR and CYP11A1 to pregnenolone to progesterone by 3BHSD and out or to 17OH-pregnenolone by CYP17 hydroxylase the DHEA by CYP17lyase then to Androstenedione by 3BHSD can go to testosterone via 17BHSD1; Adrostenedione can go out follicular fluid or ovarian vein or to the granulosa cells, testosterone to granulosa cells
How do granulosa cells synthesize estrogens?
testosterone from theca to E2 via CYP19; Androstenedione to E1 via Cyp19, E1 secreted out or converted to E2 via 17BHSD1
How do luteal cells synthesize progesterone?
LDL to cholesteryl esters to cholesterol via esterase to pregnenolone via StAR, PBR, and Cyp11A1 to progesterone via 3BHSD
Which cells have LH receptors?
theca, luteal, and mural granulosa cells of dominant antral follicle but not in small antral follicles
What enzymes are stimulated by LH in the ovary?
StAR, CYP11A1, 3BHSD, and CYP17
What enzyme is stimulated by FSH?
What organs or tissues does progesterone effect?
oviduct, uterus, breast, cervix and vagina
How does progesterone effect the oviduct?
increase secretions and decrease muscular contractions
How does progesterone effect the uterus?
increase endometrial differentiation, glycogen and glycoprotein synthesis and secretion; decrease myometrial growth and contractility
How does progesterone effect the breast?
increase development of lobuloalveolus and fluid retention in subcutaneous tissue
How does progesterone effect the cervix and vagina?
increase epithelial differentiation and thick cervical mucus, decrease epithelial proliferation
What organs or tissues does estrogen effect?
oviduct, uterus, breast, cervix and vagina, bone, larynx, liver, skin, hip/thigh, plasma cholesterol
How does estrogen effect the oviduct?
increase formation and contractility of cilia and muscular contraction
How does estrogen effect the uterus?
increase endometrial proliferation and myometrial growth and contractility
How does estrogen effect the cervix and vagina?
increase: epithelial proliferation, glycogen deposition, watery cervical mucus
How does estrogen effect the breast?
increase: proliferation of ductal epithelium, ductal growth, growth of lobulo-alveolus, and fate deposition
How does estrogen effect the bone?
increase: osteoblast activity, calcium deposition, linear growth, maturation of epiphyseal cartilage, pelvic diameter
How does estrogen effect the larynx?
long and unchanged vocal cord
How does estrogen effect the liver?
increase (thyroid and steroid binding globulins)
How does estrogen effect the plasma cholesterol?
decrease VLDL, increase HDL
How does estrogen effect the hip/thigh?
increase: lipogenesis and female type fat deposition
How does estrogen effect the skin?
increase vascularization and sebaceous secretion
What is the process of oogenesis? when does each step occur?
mitosis (1st trimester) interphase and prophase or meiosis 1 (primary oocyte, 2nd trimester), menarche occours, ovulation simtulus completeion of meiosis I (1st polar body formed, prophase 2 and metaphase 2) freeze in metaphase 2 for 24-48 hours til fertilizaition now ovum, fertilization stimulus completion of meiosis 2, 2nd polar body formed now an egg (**1n)
What happens to germ cells numbers in the ovary from inutero to puberty? How many will be ovulated? What happens to the others?
6-7 mil to 2 mil at birth to ~400K by puberty, ~450 without cycle delay; oocyte apoptosis or follicular degeneration
What is the mechanism for follicular atresia?
activation of cascade of cell death genes, relase cytochrome C from mitochondria, activation of caspases and formation of apoposome, chromosome fragmentation, deterioration of cytoplasm, cellular phagocytosis, theca cells persist and blend into stroma forming secondary interstium, occurs at any time during follicular development, critical role in screening best follicle and oocyte
What happens with sex genes during development?
active at first in fetal life for ovary development, genes in pseudoautosomal domain will be inactivated on one; in XX background with lack of antimullerian hormone, mullerian duct differentiates into female reproductive tissue, hypothalamus undergoes sex differentiation for cyclic relase of gonadotropins,
What affect can the non-disjunction chormosomes have?
result in various errors in sex differentiation
What is female pseudohermaphroditism? Where can the defects occur?
46XXDSD, female genotype and two ovaries but external genitalia show degree of virilzation,; fetal adrenogential syndrome or placentla aromatase defect or maternal influece
What enzymes are involved in adrenogential syndrome?
21-hydroylase deficiency or 11B-hydroxylase deficiency
How can the maternal side affect female pseudohermaphroditism?
maternal ingestion of progestins or androgens or maternal virilizng tumor
What is turner syndrome?
45XO, characterized by streak gonads
How is GnRH secretion regulated?
B-adrenergic receptor via NE increases pulse amplitude, NPY stimulation increases GnRH pulse frequency and amplitude, Trans-synaptic GABA and B-endorphin inhibition POMC neurons, which are stimulated by P and E, decrease pulse frequency
What is the mechanism of action of GnRH?
binds to cell surface receptos, ligand receptor complex activates intracellular PKC via Ca-calmodulin and DAG
What effect does prolonged stimulation of GnRH (long acting agonists) have?
chronic down-regulation of GnRH receptor leading to suppression of gonadotropin secretion
How is GnRH used clinically?
agonists or antagonists are used for endometriosis, PCOS, and infertility (controlled ovarian hyperstimulation)
What is puberty?
activation of hypothalamic-pituitary-gonadal axis, usually begins 8-10 , culminates in menarche at 12-13
What are the characteristics of the onset of puberty?
adrenarche- maturation of zona reticularis (CYP17ahydroxylase), activation of HPO axis, and gonadarche- gonadal development
What things can affect onset of puberty?
nutrition (obesity causes early onset deu to extragonadal aromatization of androgens-leptin, malnutrition delays), health (poor due to diseases can delay), or socioeconomic (related to above 2)
What occurs during adrenarche?
7-8 years prior to onset of puberty adrenal androgen (DHEA and DHEAs and adrostenedione) secretion starts increasing and reaches maximal values by 13-15, 2 yrs b4 peak of gonadotropins and ovarian steroids, plasma andrenal androgens reach high levels, these induce sex hair development, axillary 2 yrs after pubic
What occurs during the activation of HPO axis?
puberty onset due to maturation of GnRH neurons; enhanced excitatory and reduced inhibitory neural inputs, increased activity of GnRH neurons and consequent low and non-pulsatile release on GnRH, low levels of plasma FSH and LH; GnRH intiates spontaneous low pulsatile firing, pituitary increases more FSH and LH secretion is pulsatile and nocturnal
What is the state of GnRH neurons during prepubertal period? How?
suppressed from higher sensitivity of GnRH neurons to neg feedback of estrogen or strong influences exerted by inhibitory NT (GABA and B-endorphin);
What in the ovaries change during puberty?
recruitment of antral follicles, selection of dominant follicle and ovulation, production of estrogens (E1 and E2), progesterone and androgen
How do the follicles develop through puberty?
develop beyond small antral class, synthesize E2 and inhibin, rising E2 stimulates endometrial growth but incomplete (spotting, anovulatory and irregular menses), recurrent E2 action synchronizes GnRH neurons, induces more GNRHR in gonadotropes, graafian follicle secretes high levels of E2, blood levels increase (~36 hrs)-> initiation of pit release of LH-> follicular progesterone secretion-> maintenance of E2 effects on NPY neurons for high amplitude GnRH secretion and increased pituitary sensitivity to GnRH; high E2 >50hours-> positive feedback at pituitary->synthesis of GnRH receptors on gondaotropes, at NPY level-> increased GnRH from nerve temrinals, LH surge induces ovulation
What are the utero vaginal changes during puberty?
increase uterine weight followed by endometrial proliferation, glycogen deposition and vascularization, differentiation of endocervical glands and secretion of watery mucus w/ glycogen, growth of oviducts, proliferation of cilia and increase contractility, vaginal length increases, epithelium becomes cornified, clitoris and labia enlarge
What function does the glycogen rich mucus play in the vagina?
allows growth of lactobacillus acidophilus, secrete lactic acid in upper vagina near cervix, keeps pH low and prevents growth of pathogens in the cervix
What physical changes occur to the body during puberty?
body fat increases 120% and lean body mass by 44%, spurt stimulated by E2, GH, IGF-1 and thyroid also important, GH and IGF-I induce peripheral resistance resulting in increase in serum insulin which maintains the effects of IGF-I and E2 on linear growth, AA transport and FA deposition by reducing IGF-IBP1 and SHBG
Where does pubertal fat deposition occur?
hip, thighs, and mons pubis
How is bone length increased during puberty?
activities of osteoblasts and chondrocytes, more Ca and PO4 deposition, and collagen synthesis
What marks the cessation of body growth during puberty?
estrogen induced ossification of epiphyseal cartilage
What occurs in tanner stage II of thelarche? age range?
breast bud, mound of subareoar tissue less than or equal to diameter of enlarging areola; 8.9-12.9
What occurs in tanner stage III of thelarche? age range?
enlargement with diameter greater than that of areola, 9.9-13.9
What occurs in tanner stage IV of thelarche? age range?
projection of areola and papilla and formation of a secondary mound above the plane of the breast, 10.4-15.3
What occurs in tanner stage V of thelarche? age range?
adult, projection of papilla only, areolar border in plane of breast, 11.3-16.8
What occurs in tanner stage II of puberche? age range?
sparse growth of long, straight or slightly curled hair on pubis or labia, 9-13.4
What occurs in tanner stage III of puberche? age range?
rim of coarse dark, uncurled hair confined to lower pubis, 9.7-14.1
What occurs in tanner stage IV of puberche? age range?
adult type sexual hair confined to inverted suprapubic region, 10.4-14.8
What occurs in tanner stage V of puberche? age range?
adult distribution with spread to medial aspects of the thighs, 12.4-16.8
What causes oily secretions from sebaceous glands and prevents acne formation?
What causes precocious puberty?
early activation of GnRH pulse generator, HPOaxis or ectopic GnRH producer, premature secretion of FSH and LH by pituitary tumors, high estrogen resulting from granulosa cell tumor, ingestion of estrogenic substances, excess adrenal androgens and extragonadal conversion to estrogen
What are the causes of delayed puberty?
idiopathic, hypogonadotropic hypogonadism, craniopharyngeoma, genetic defect, ovarian failure, exercise and inadequate calorie intake
What causes idiopathic delayed puberty?
lesions in CNS and delayed activation of GnRH pulse generator
What causes hypogonadotropic hypogonadism?
congenital absence of GnRH neurons (Kallmann syndrome (also have a olfactory deficiency due to failure of cellular migration in utero
What is a craniopharyngeoma?
pituitary damage due to pressure
What genetic defects cause delayed puberty? What is seen clinically?
Turner syndrome (45,X)- no gonadal development in complete absence of short arm of X-chromosome, minimum deletion- a few small follicles develop during puberty, usually irregular menses, follicle induction by FSH in IVF and pregnancy is not recommended
What causes delayed puberty due to ovarian failure?
radiation damage or chemotherapy