1
Q
Follistatin
A
Testicular Peptide hormones
-inhibits activins and inhibing
2
Q
Activins
A
Testicular Peptide hormones
- produced in sertoli cells
- stimulate FSH beta-subunit production
3
Q
Inhibins
A
Testicular Peptide hormones
- produced in seminiferous tubules and sertoli cells
- suppresses FSH secretion
- injury to seminiferous leads to elevated FSH
4
Q
Primary Hypogonadism
A
-failure of testes
5
Q
Secondary Hypogonadism
A
-non-testicular condition including hypothalamic and pituitary diseases
6
Q
Hypothalamic disorders
A
-low GnRH leads to failed LH and FSH production
7
Q
Pituitary disorders
A
-low LH and/or FSH production leads to failed testosterone production and/or spermatogenesis
8
Q
Gonadal Disorders
A
-failure of testosterone production from Leydig cells and/or spermatogenesis, no feedback leads to elevated LH and FSH
9
Q
Post-Gonadal Disorders
A
-defects in testosterone receptor function
10
Q
Kallman’s Syndrome
A
Hypothalamic Disease - inappropriately ‘normal’ LH and FSH with low testosterone
-anosmia
11
Q
Prader-Willi Syndrome
A
Hypothalamic Disease - inappropriately ‘normal’ LH and FSH with low testosterone
-obesity, hyperphagia, hypotonia, micropenis, small hands & feet
12
Q
Lawrence-Moon Syndrome
A
Hypothalamic Disease - inappropriately ‘normal’ LH and FSH with low testosterone
-retinitis pigmentosa polydactyly
13
Q
Fertile Eunuch Syndrome
A
Pituitary Disease - nappropriately ‘normal’ LH and FSH with low testosterone
-LH deficiency
14
Q
Pre-pubertal Gonadal Failure
A
- small testes, phallus, & prostate
- delayed puberty
- scant pubic and axillary hair
- disproportionately long arms & legs (delayed epiphyseal closure)
- Reduced male musculature
- Gyneocomastia
- Persistently high-pitched voice
15
Q
Post-pubertal Gonadal Failure
A
- progressive decrease in muscle mass
- loss of libido
- impotence
- oligospermia or azoospermia
- occasionally, menopausal-type hot flushes (with acute onset of hypogonadism)
- poor ability to concentrate
16
Q
Evaluation of hypogonadal patient
A
History: sexual function, family, fertility status
Physical Exam: arm span to height, axillary/pubic hair, phallus and testes
Lab: Test. FSH, LH, Prolactin, Karyotyping
Provacative Testing: GnRH stimulation, Clomiphene stimulation, hCG stimulation
Pituitary MRI
17
Q
Isolated FSH Deficiency
A
Pituitary Disease - nappropriately ‘normal’ LH and FSH with low testosterone
18
Q
Hyperprolactinemia
A
Pituitary Disease - nappropriately ‘normal’ LH and FSH with low testosterone
-inhibited GnRH release and libido
19
Q
Hemochromatosis
A
Pituitary Disease - nappropriately ‘normal’ LH and FSH with low testosterone
-loss of LH and FSH (also effects testes directly and can cause a primary hypogonadism)
20
Q
Testicular Diseases
A
High LH and FSH due to absent feedback of testosterone
- bilateral anorchia (vanishing testes syndrome)
- chyptorchidism
- sertoli cell only syndrome
- myotonic dystrophy
- gonadotoxins
- chemo
- radiation
- orchitis (mumps)
- systemic illness
- hemachromatosis
21
Q
Testosterone
A
- levels vary from hour to hour
- normally highest levels in the early morning hours
- circulating bound to sex hormone-binding globulin (SHBG) and albumin
- only ~2% of total hormone is free for biological availability
- normal total test. can be seen in bypogonadal patients with increased SHBG in whom the available test. is truly low
- SHBG increase about 1% per year with aging
- equilibrium dialysis measures of free test. are most accurate
22
Q
What can cause low SHBG?
A
hypothyroidism, acromegaly and obesity
23
Q
Gonadotropins
A
- LH and FSH are both released in pulsatile fashion
- LH has a shorter plasma half-life than FSH and single low measures may be misleading
- biologic activity is affected by post-translational glycosylation and 2-site radioimmunometric assays yeild results with correlate well with biologic activity
24
Q
Prolactin
A
- unusual in that it is tonically secreted and requires dopaminergic signaling from the hypothalamus to down-regulate its release
- directly down-regulates release of FSH and LH
- directly decreases libido independent of testosterone levels
25
Semen Analysis
- primary test to assess fertility potential of male
- should be collected after 2-5 days of abstinence and evaluate within 2 hours
- volume should range from 1.5-6mL
26
Fertile Sperm Sample
- motility of more than 50%
| - sperm count that exceeds 20 million/mL
27
Klinefelter's Syndrome
- chromosomal disorders
- XXY
- tall, gynecomastia, eunuchoid habitus, MR common
28
XYY
- chromosomal disorders
| - oligo/azospermia
29
Noonan's Syndrome
- chromosomal disorders
- XO
- phenotypically similar to Turners patients but male
30
XX Male Syndrome
- chromosomal disorders
| - normal height, no MR, azospermia
31
Male primary sex organ?
-testes
32
Testes
1) located in scrotum (temp. regulating system)
2) need temp <37C for optimal spermatogenesis
3) blood supply via pampinoform pelxis (countercurrent heat exchanger)
4) testicular movement: cremaster muscle
5) scrotal movement and sweating
33
Secondary Sex Organs
1) genital tract
| 2) accessary glands
34
Genital tract
epididymis, vas deferens, ejaculatory duct, urethra (and penis)
35
Accessary glands
- bulbourethral glands
- seminal vesicles (60% of seminal volume, contains prostaglandins, fructose, cirtic acid)
- prostate (20% seminal volume)
36
Permanence/reversibility of pubertal changes
- (by dec. gonadotropin or androgen secretion)
| - spermatogeness, size, secretions, content (fructose, citrate) or sex accessor glands
37
Changes that are not reversible
-voice or height
| slow is beard growth, libido, muscle mass
38
What do testes have?
- seminiferous tubules
- produce gametes (sperm)
- intersitial (Leydig) cells
- produce testosterone
39
Spermatogenesis hormones required
1) TSH
2) Testosterone: high concentrations
- indirectly require LH for test. and GnRH for FSH and LH
40
Sertoli Cell Functions
1) stimulate spermatogenesis (site of action of FSH and test)
2) "Nourish" developing sperm
3) Provide blood-testis barrier to may chemicals
4) Produce hormone inhibin that feeds back negatively to dec. FHS
5) Secrete luminal fluid; includes androgen binding protein (ABP)
6) Phagocytosis of: dead or defective developing sperm excess cytoplasm from developing sperm
41
Testosterone production is stimulated by?
LH (pulsatile ~1.5hr)
- secretion is pulsatile
- but seems steady in comparison to female sex hormones over month
42
Metabolism of Testosterone
-activation in some target tissues it must be metabolized to dihydrotestosterone (DHT) in order to reach nucleus and prodcue androgenic actions
43
Processes that do NOT require transformation of hormone to be active in nucleus?
- pubertal growth of skeletal muscle, penis, scrotum
| - libido
44
Metabolism/Excretion of Testistrone
- degraded by liver
- metabolites excreted in urine (sulfated and glucuronated)
- excreted as 17-ketosteroids
45
Transport of Testosterone
-In blood
46
Actions of Testosterone
- fetal differentiation of male accessory organ
- change in tissues at puberty, some permanent
- maintain size & function
47
Regulation of Pituitary-Testicular Axis
1) always negative feedback
| 2) test: both hypothalamus dec. GnRH (inc. interval b/w pulses) and pituitary (mainly dec. LH, weaker dec. of FSH)
48
Primary Female Sex Organ
ovary
49
Ovary
-located in abdomen (function well at body temp)
50
Female Secondary Sex organs?
Genital Tract: oviducts (fallopian tubes), uterus, vagina
| Accessary glands: mucus glands, (mammary?)
51
Functions of Estrogen
1) stimulates growth and hormonal secretion of both the ovaries and the follicles that produced the estrogen, particularly in the "dominant follicle"
2) - and + feedback effects on hypothalamus and anterior pituitary (on GnRH, FSH, LH)
3) produce female configuration of body
- hip widening, fat amount, distribution
4) Stimulates: growth, motility, and secretions of muscle and endothelial surface of oviducts, uterus, vagina
52
Thecal Cells
like leydig cells
-make androgen
with high areomatiase activity, estrogens are made
53
Granulosa Cells
like sitori cells, around ovum, on inside
54
Low Estrogen does what?
-inhibits on LH and FSH
55
Rising Estrogen does what?
-stimulatory LH and FSH leads to mid-cycle LH surge that causes ovulation
56
Very high Estrogen does what?
-inhibitory (was used as birth control, not now b/c side effects of E)
57
Very low Estrogen + Progesterone
moderate does, inhibitory
| -used in birth control
58
Oviducts
- increase
| 1) growth of muscle and epithelium
59
Estrogen effects on uterine endometrium
- growth, blood supply, endometrial glands
| - induces progesterone receptors in the uterine endometrium
60
Estrogen effects on growth?
- long bone growth, causes epiphyseal cartilage plates of long bones to "close", thus halts height growth
- BUT initially, estrogens stimulate height growth
- promotes growth of female external genitalia
61
Effect of estrogen on bone loss?
reduce it
62
Actions of Progesterone
1) Uterine Muscle: inhibitory
2) Endometrium: Stimulatory
3) Pituitary - inhibits LH & FSH secretion, especially low estrogen present
4) Stimulates mammary gland growth, especially the milk producing glands, inhibits Prl (or hPL) stim. of milk synthesis
5) Raises body temperature: rise in BBT beginning a few days post-ovulation
6) production of thick, sticky cervial mucus
63
Uterine muscle Progesterone
- decreases motility and prevents contractions from being coordinated
- antagonizes estrogen's enhanvement of motility
- partly by dec. # of estrogen receptor (on smooth muscle on female tract)
- decreases sensitivity to oxytocin
- hyperpolarizes muscle membrane (makes it less excitable)
64
Endometrium: stimulatory - Progesterone
- after priming of tissue with estrogen, progesterone stimulates secretion by endometrial glands lining the uterus
- this prepares uterus for implantation
65
Thick Cervial Mucus
1) dec. chance of other sperm to get into uterus
| 2) provide barrier to potentially damaging microorganisms from getting into uterus and into the develping fetus
66
To get pregnant, at least several sperm must...
- survive in vagina
- penetrate the cervical os (1/2000)
- become capacitated
- move up uterus (1/5000)
- go into the "correct" oviduct (1/10,000)
- move up the ovidict-fertilization usually occures in upper oviduct
- peretrate zona pellucida
67
Survival of Ovum
6-12 hrs
68
Survival of Sperm
1-2 days
69
Sexual interest in men?
always
70
Sexual interest in women?
- mid cycle (ovulation)
| - pre-menstration
71
Lots of Sperm: ejaculation
volume: 1-3ml
conc: 100mill/ml
total # 100-300 million
72
What helps to get sperm to egg?
- thinning of cervical mucus from estrogen
| - motility of female tract is increased by: estrodiol, prostaglandins, oxytocin
73
How many germ cells at birth?
1 million, most >70% regress before puberity
74
How many eggs are ovulated?
400-450 over next 35 years, the rest start to grow and then degenerate
75
When all eggs are gone?
-menopause, no more ovulation, decline in estrogen level, increase in LH and FSH secretion
76
What is ovulation triggered by?
-mid-cycle surge of LH (probably FSH is not needed for ovulation)
77
Ovulation
1) mid-cycle surge of LH
2) follicular membrane ruptures after attack of proteolytic enzymes
3) Some local bleeding may occur, some pain may be felt ("mittleschmerz")
4) variation in length of a women's menstrual cycle is caused by the length of the follicular phase, time for follicle to develop and the ovum to be released
78
Luteal Phase
1) the Corpus Luteum (CL) develops from follicular cells, starting shortly before ovulation (small inc. in progesterone near end of follicular phase)
2) the CL secretes estrogen, lots of progesterone, 17-hydroxyprogesterone, and inhibin
79
How long does luteal phase last?
-2 weeks (but CL is degenerating in last 5 days)
80
Regulation of Menstrual Cycle
-correspondance of events in ovary and uterine endometrium
81
Importance of Ovary in regulation of cycle timing?
- only need to have
1) a functional ovary (or 2)
2) hypothalmo-hypophyseal portal system intact
3) pituitary gonadotropes
4) GnRH pulses
82
Shorter Luteal Phase in women?
- started sudden heavy exercise program
- infertile women
- women who have had first trimester miscarriage
83
Bone conditions considered to be metabolic bone disorders?
- osteoporosis
- paget's disease of bone
- osteomalacia in adults and rickets in children
- osteoitis fibrosa cystica
84
Bone Remodeling
- bone remodeling maintains a healthy skeleton
- bone remodeling includes removing of old bone and replacing it with new bone
- imbalance of bone remodeling results in metabolic bone disease
- bone remodeling can be biochemical markers of bone resorption and formation
85
Risk Factors for Fracture
Age: major contributor to fracture risk
Gender: W > M
Bone Mineral Density
Body Mass Index
86
Lifestyle Risk factors of Osteoporosis
- alcohol abuse
- smoking
- immobilization or inadequate physical activity
- excessive thinness
- high salt intake
87
Nutritional Factors of Osteoporosis
- low Ca intake
- low vit D intake
- excess vit A intake
88
GI disorders of Osteoporosis
- Celiac Disease
- Gastric Bipass
- GI surgery
- Inflammatory Bowel Disease
- Malabsorption
- Pancreatic Disease
- Primary biliary cirrhosis
89
Hormone abnormalities of osteoporosis
- hyperparpthyroidism, primary/secondary
- low T or androgen insensitivity
- low estrogen during menopause or associated with athletic amenorrhea, premature ovarian failure, premature menopause, hyperprolactinemia or hypopituitarism
- excess cortisol, secondary or primary
- thyrotoxicosis
- diabetes type I or II
- adrenal insufficiency
90
Genetic Factors of Osteoporosis
marfan syndrome
| hemachromatosis
Endocrinology
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