V410 Exam I Flashcards
(145 cards)
(L18) Reproductive hormones are classified as either species-specific or conserved in their structure. Which groups of hormones are species-specific?
The glycoproteins (FSH, LH, inhibins, AMH, and eCG) The polypeptide hormones (prolactin, GH)
(L18) Species-specific hormones are clinically important for three reasons. What are they?
- The protein/glycoprotein hormones from one species cannot be used therapeutically in another since the expected effects may vary.
- Even if an effect can be elicited, the host’s immune system can mount a response against the foreign protein hormone.
- Diagnostic assays for protein hormones are also species-specific, preventing general use.
(L18) Reproductive hormones are classified as either species specific or conserved in their structure. Which groups of hormones are conserved?
The small peptide hormones (GnRH, oxytocin)
The steroid hormones (testosterone, estrogen, progesterone)
The prostaglandins (PGF2-a)
(L18) What is the basic structure of glycoprotein hormones?
Glycoprotein hormones are composed of an alpha and a beta chain. The alpha chain is shared between LH and FSH, whereas the beta chain confers specificity. Additionally, the level of glycosylated sites on the subunits grant an additional level of specificity.
(L18) Compare equine CG and LH.
Equine chorionic gonadotropin (eCG) has the same exact alpha and beta subunits as equine LH. They differ in two ways - where they’re secreted and the extent of glycosylation of their subunits. eCG is secreted by the chorion of the fetus, while eLH is secreted by the anterior pituitary. Additionally, eCG is far more glycosylated than eLH, increasing its half-life.
(L18) Biochemically, how are sex steroid hormones synthesized?
Steroid hormones are derivatives of cholesterol in which the 27 carbon structure has been cleaved into 21, 19, and 18 carbon structures. The 21 carbon hormone, pregnolone, is the precursor to the sex steroids (19 carbon androgens and 18 carbon estrogens) and 21 carbon gluco- and mineralocorticoids.
(L18) Sex steroids and small peptide hormones are conserved across species, generally making them effective therapeutics. In what situation would small peptide hormones not be effective?
Chronic overexposure of receptors to these hormones downregulates these hormones, inhibiting LH and FSH release. This results in chemical castration. GnRH and oxytocin’s efficacy is determined by how their signal is received. Normally, pulsatile release of GnRH stimulates pulsatile release of LH and FSH from the anterior pituitary gland.
(L18) Sex steroids and small peptide hormones are conserved across species, generally making them effective therapeutics. Generally, what occurs with chronic stimulation of sex steroid receptors?
Steroid receptors bind to nuclear receptors that do not exhibit downregulation when chronically stimulated. Unlike small peptide hormones, chronic steroid stimulation causes hyperplasia of the target tissue.
(L18) Are diagnostic assays more effective for protein hormones or steroid hormones? Why?
Conserved steroid hormones.
(L18) There’s a lot of variation in hormone concentrations within an individual and over time. What kind of test reduces this variability?
A response test minimizes the variability inherent to a single blood sample. With a response test, something like GnRH is administered, and there should be an expected increase in LH and testosterone soon after.
(L18) Equine chorionic gonadotropin is a therapeutic stimulator of follicular growth when given to other species. Why?
eCG, because of its structure, binds to LH receptors in the horse. However, when administered to another species e.g. the dog, eCG binds to FSH receptors, not LH receptors. This induces stimulates follicular development.
(L19) What are the 4 basic levels of sexual determination?
Chromosomal - XX or XY
Gonadal - ovaries or testes
Somatic - mullerian ducts/uterus/vagina or wolffian ducts/scrotum
Hypothalamic
How could an XX or an XY individual have the gonads of the opposite sex?
Several genes have been identified e.g. SRY (the sex-determining region of the Y chromosome) and Fox L2 that appear to control gonadal differentiation. However, these genes have been identified as part of complex signaling cascades with other genes, and issues with any step along these pathways will disrupt normal gonadal development.
(L19) The genital ridge contributes to gonad development. How?
Primordial germ cells from the yolk sac populate genital ridge’s cortex and medulla during embryological development. XY-associated signaling causes the cortex to regress, while the medulla remains to form the testes. XX-associated signaling does the opposite - the cortex survives while the medulla degenerates.
(L19) How does the male internal genitalia develop?
The testes secrete two hormones associated with internal genitalia development - AMH from Sertoli cells and testosterone from Leydig cells. Testosterone binds to androgen receptors on mesonephric ducts/Wolffian ducts to stabilize them. AMH causes regression of the paramesonephric ducts/Mullerian ducts.
(L19) How does the female internal genitalia develop?
The female internal genitalia develops in the absence of hormones because fetal ovaries are endocrinologically inactive. Wolffian ducts regress because there’s no signal for stabilization, while the Mullerian ducts persist because there’s no signal for regression.
(L19) How does the male external genitalia develop?
Male external genitalia development depends on the conversion of testosterone into DHT by 5-alpha-reductase. DHT then stimulates the formation of the penis and scrotum.
(L19) How does the female external genitalia develop?
Female external genitalia develop in the absence of DHT. The tissues that would form the penis and scrotum instead form the vagina and clitoris.
(L19) How would an XX individual develop internal and/or external male genitalia?
Female fetuses express the same androgen receptors and 5-alpha-reductase as males do. Exposure to androgens or AMH masculinizes the female fetus. Testosterone will stabilize Wolffian ducts and AMH would cause regression of the Mullerian ducts. Even low levels of testosterone, when converted to the more potent DHT, would induce development of external male genitalia (in the absence of Wolffian ducts).
(L19) What are true hermaphrodites?
True hermaphrodites express both type of gonadal tissue. This can manifest as either one of each type of gonad or an ovotestis.
(L19) What are pseudohermaphrodites?
A pseudohermaphrodite expresses one gonad type but the internal/external genitalia of the other sex.
(L19) What is true sex reversal?
A sex reversed individual will express one karyotype but the gonad type of the other sex.
(L19) Describe what happens with androgen resistance syndrome.
Androgen resistance syndrome is defined as a dysfunctional gene that encodes the androgen receptor. The gene is found on the X chromosome, so a female carrier may potentially pass it onto some of her male offspring. Affected males will express gonads (as determined by their karyotype) but will have Mullerian ducts, no Wolffian ducts, and female external genitalia.
(L19) What occurs with a 5-alpha-reductase deficiency?
Males, without enough 5-alpha-reductase, will express Wolffian ducts but will have external female genitalia.