Physio 10 Flashcards
gonadal sex for males
SRY gene encodes testis determining factor (TDF), a transcripion factor. When SRY is present, indifferent gonad becomes testes and germ cells develop into spermatogonia
genotypic sex for males
Y chromosome = male
Phenotypic sex for males
hormones produced by the gonads determine the phenotypic sex. Includes development of accessory sex organs, external genitalia that require the presence of dihydrotestosterone, and secondary sex characteristics
XX male
in rare cases, the SRY gene translocates to the X chromosome. the ovum receiving the X chromosome with the SRY gene will develop into a male. crossing over between X and Y can leave an X chromatid with a substantial portion of the testis determining factor region and a Y without TDF.
what do androgens made by the leydig cells promote?
differentiation of the wolffian duct, and prostate development
primordial gonad
contains the germ cells. the genotype of the germ cells determines the fate of the gonad. considered indifferent before it differentiates into testis or ovaries.
differentiation of the testes in males
mesonephros develops into the epididymis. wolffian duct develops into the vas deferens, seminal vesicles, and ejaculatory duct. mullerian ducts degenerate due to anti-mullerian hormone from sertoli cells
differentiation of the external genitalia
in the absence of testosterone, the undifferentiated external genitalia develop into the female structures. testosterone, after conversion to dihydrotestosterone, stimulates the formation of male external genitalia. begins at 10 weeks of gestation
hypothalamic-pituitary-gonadal axis function and stuff
regulates spermatogenesis and androgen production. GnRH stimulation and FSH and LH release are all pulsatile. constant levels of GnRH prevents LH and FSH release. products of the testes have a negative feedback on the hypothal and anterior pituitary.
prenatal stage of development
leydig cells make up more than half the testes. increase in leydig cells is dependent on maternal chorionic gonadotropin (hCG) in early development and embryonic leutinizing hormone, LH, in late development
prior to puberty development
few GnRH pulses and low FSH and LH levels. hypothal and pituitary are very sensitive to negative feedback inhibition by androgens. spermatogonia exist in diploid, undifferentiated form in basal compartment of testes
puberty development
frequency and amplitude of GnRH pulses increase. sensitivity of HP axis to negative feedback of testosterone decreases. gonadotroph sensitivity to GnRH increases, LH and FSH production increases. testosterone increases and spermatogenesis begins. androgen driven changes characteristic of puberty occur
physiology of leydig cells
has receptors for LH. stimulates G protein coupled receptor to make cAMP and activate PKA. this increases transcription of enzymes involved in testosterone synth, stimulates rate limiting step (cholesterol to pregnenolone), and sterol carried protein and sterol activating protein.
Sertoli cell physiology
has receptors for FSH. increases transcription of androgen binding protein which keeps local testosterone levels high, P450 aromatase to produce estrogen, growth factors that support production of sperm, inhibins that suppress leydig cell proliferation and FSH secretion, and factors that act on leydig cells
crosstalk between leydig and sertoli cells
leydig cells make testosterone which acts on sertoli cells. leydig makes endorphin which inhibits sertoli cell proliferation. sertoli cells make estrogen which acts on the leydig cells. sertoli cells make growth factors which acts on leydig cells to increase LH receptors
kallmann syndrome
hypogonadotropic hypogonadism. lack LH and FSH and have anosmia (inability to smell). patients fail to enter puberty. Genes KAL-1, FGFR1, PROK2, and PROKR2 have been implicated in the disease. mutations prevent neurosensory neurons extending from axons into the brain which prevents migration of GnRH neurons into the hypothalamus
androgen synthesis
cholesterol is precursor. made from acetyl coA or taken up from LDL. first step occurs in mitochondria, where P450 side chain cleavage enzyme (desmolase) removes the side chain of cholesterol and produces pregnenolone. this is the rate limiting step and is upregulated by LH.
male pseudohermaphroditism
any deficit in the mechanism by which androgens act in genetic males may cause this. potential cause is 5alpha reductase deficiency. this makes dihydrotestosterone (DHT). problems with the enzyme lead to low DHT but normal testosterone. Leads to a failure in DHT dependent development, aka urogenital sinus and external genitalia. develop according to female pattern. wolffian ducts degenerate. normal AMH suppresses mullerian development
androgenic effects in general
maturation of sex organs, particularly the penis.
development of secondary sexual characteristics like deepening of voice, growth of beard and axillary hair.
promote protein synth and tissue growth
increase in muscle and strength, bone density and strength, nd maturation
males have larger hearts, lungs, liver, and erythrocytes
androgen receptors
free form of testosterone enters cell by diffusion. binds homodimereic receptor. directs transcriptional activity of target genes. DHT binds the same receptor but has greater activity.
kennedy’s disease aka spinobulbar muscular atrophy (SBMA)
lower motor neuron disease caused by mutation in the androgen receptor. expansion of a CAG repeat in the gene causes a polyglutamine expansion in the androgen receptor. mutation causes a toxic gain of function. patients display progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord.
senescence (andropause)
unlike menopause, no abrupt loss of fertility. testosterone decreases with age especially >40 years. quantity and quality of sperm decreases. FSH and LH increase. reduced testosterone causes some aging problems: decreased bone, muscle mass, apetite, libido, hematocrit.
low testosterone
low sex drive, ED, loss of muscle, mood problems, sleep problems, loss of body/facial hair. high percentage of men with symptoms benefit from treatment. men with prostate or breast cancer should not be treated with testosterone.
finasteride (propecia)
blocks production of DHT. used to treat male pattern baldness. side effects include impotence, depression, abnormal ejaculation
