SPONTANEOUS and INDUCED

Most mammals are spontaneous

Most vertebrates are induced

Estrus cycle= spontaneous

Example of induced= spadefoot toads: come out from the ground when there is rainfall and temperature is 10 degrees C.

Females ovulate on the way to the pond.

The 2 phases in seasonal breeders

The effect of a thyroidectamy on these phases.

1. GONADAL RECRUDESCENCE= growth of gonads

2. GONADAL REGRESSION

Thyroidectamy --> no gonadal regression

**TypeII deiodinase in hypothalamus critical for termination of seasonal breeding

Reproduction hormones from the...

Hypothalamus:

Pituitary:

Gonads:

Hypothalamus: GnRH, GnIH, Kisspeptin (stimulates GnRH secretion)

Pituitary: LH, FSH, PRL (stimulates lactation and inhibits LH and FSH at potuitary)

Gonads: Androgens, estrogens, progestins,

gonadal peptides: Inhibin, Activin, follistatin (also made in the pituitary)

1st biologically active sex steroid (gives rise to the rest)

What kind of steroid is it?

PROGESTERONE

C21 steroid= progestins

RU486 or MIFEPRISTONE

Progesterone and glucocorticoid receptor blocker

What kind of steroid are the androgens?

What are all of the different androgens?

C19 STEROID

TESTOSTERONE

5α-DIHYDROTESTOSTERONE (DHT)

ANDROSTENEDIONE

DIHYDROEPIANDOSTERONE (DHEA, DHEA-S)

***

T converted to DHT in target tissues by 5α-reductase enzyme (2 forms - II more important - made in the prostate)

T, DHT, and androstenedione made by GONADS

CYPROTERONE ACETATE

SPRINOLACTONE - also blockes mineralocorticoid receptors

***

Block androgen receptors and lose negative feedback on gonadotrophins - LH and FSH will be produced in excess

What kind of steroid are estrogens?

What are estrogens generated from? and by what?

C18 STEROIDS

17-BETA-ESTRADIOL

Generated from ANDROGENS (T, androstenedione, DHEA) by aromitization by AROMATASE

***

DHT NOT AROMATIZABLE!

TAMOXIFEN= E2 receptor blocker...though can have some agonist effects...

FADRAZOLE= Aromatase inhibitor

INHIBIN inhibits FSH secretion --> blocks oocyte maturation and follicular development.

NO effect on LH.

Generally produced by mature ovarian follice.

ACTIVIN stimulates FSH secretion.

Produced inside the pituitary (role as a hemocrine factor is unknown).

FOLLISTATIN = Activin binding protein

Inhibits FSH release by binding activin.

Expressed both in the gonads and pituitary.

TRANSACTING GROWTH FACTOR BETA SUPERFAMILY

(TGFβ SUPERFAMILY)

Comprised of 3 different subunits that are mixed and matched: α_A (18-20K), β_A (14K) , β_B (14K)

INHIBIN A= α_A+ β_A

INHIBIN B= α_A + β_B

ACTIVIN= β_A + β_B

***

Inhibin B is most important form made by gonads!

Where are the GnRH neurons in humans and about how many of them?

Where is GnRH released?

GnRH neurons in the ARCUATE NUCLEUS and there are ~1000

GnRH released into the PITUITARY PORTAL SYSTEM (MEDIAN EMINENCE)

***

GnRH neurons must migrate to the arc from the OLFACTORY REGION all the way to the BASAL FOREBRAIN

Disruption of this migration --> disruption of reproduction function

NOT DIRECT ONTO GnRH NEURONS

T --> GnIH --| GnRH neurons

E2 --> GnIH --| GnRH neurons

P4 --| KISS1 NEURONS --> GnRH neurons

(P4 inhibits Kisspeptin which normally stimulates the release of GnRH)

When does the pulsitility of GnRH favor LH and when does it favor FSH?

How does continuous secretion of GnRH affect gonadotrophins?

1 PULSE/1 HOUR --> LH

1 PULSE/3 HOURS --> FSH

Constinuous exposure to GnRH --> SUPPRESSION OF LH AND FSH

Continuous GnRH causes GnRH neurons to internalize their receptors

***

Exploited in in vitro fertalization - first repress woman's own pituitary function and then inject with LUPRON (= more stable GnRH agonist).

18hrs --> SUPPRESSION then small increase upon removal of E2 transplant

24hrs --> SUPPRESSION then small increase upon removal of E2 transplant

36hrs --> dramatic SURGE in LH

48hrs --> dramatic SURGE in LH even before removal of E2 implant!

LH SECRETION

INCREASED SENSITIVITY TO GnRH BY ADDING RECEPTORS

Kisspeptin originally called...

What is the Kisspeptin receptor and where are they expressed?

Mutations in the receptor -->

Kisspeptin originally called METASTATIN

Receptor= GPR54 expressed on GnRH NEURONS

Mutations in GPR54 --> IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM (IHH)

= FAILURE TO INITIATE PUBERTY

GnIH

KISSPEPTIN

FALSE - Some GnIH neurons project to the MEDIAN EMINANCE and release straight into the portal system and can have DIRECT EFFECTS ON THE PITUITARY

***

GnIH discovered by Kazu Tsiutsui in quail

How do the following affect LH and FSH secretion:

GnRH

Kisspeptin

T, E2

GnIH

Inhibin

Activin

Follistatin

LH                                          FSH

GnRH (+) if pulse/hour                        GnRH (+) if pulse/3hours

Kisspeptin (+)                                   Kisspeptin (+)

T,E2 (-)...sometimes E2 (+)                 Inhibin (-)

GnIH (-) direct on pituitary                  Activin (+)

                                                      Follistatin (-)

                                                      GnIH (-)

Gonachoristic species

Hermaphroditic species

Gonachoristic species= SEPARATION of gonads into separate sexed individuals

**Either GENOTYPIC (GSD) or ENVIRONMENTALLY (ESD) determined.

Hermaphroditic species= Individuals have BOTH TYPES OF GONADS but CANNOT SELF-FERTILIZE

**SEQUENTIAL HERMAPHRODITES= have the ability to change sex

PROTOGYNOUS= FEMALE-->MALE

PROTANDROUS= MALE-->FEMALE

3 Methods of producing young

Methods of fertilization

VIVIPARITY= live-bearing

OVIPARITY= egg layers

OVOVIPARITY= egges retaine w/in hatch in oviduct

EXTERNAL - amphibians, fish

INTERNAL - mammals, birds, reptiles; some amphibians, fish

Fertilization-->

Gonad determining genes-->

Gonadal formation-->

Hormones-->

sexual differentiation of phenotype

Female urogenital tract= MULLERIAN DUCT

Male urogenital tract= WOLFFIAN DUCT

SRY gene on Y chromosome important for formation of testes - once testes formed, secrete T which causes production of ANTIMULLERIAN HORMONE (AMH) aka MULLERIAN INHIBITING SUBSTANCE

which leads to regression of the Mullerian duct.

***

Female is the DEFAULT sex - LACK of hormones leads to devlopment of Mullerian duct...developing ovary do not make much steroid. Wolffian duct REQUIRES T.

Can produce adult with masculinized phenotype

***

Defect in placental aromatase can cause this exposure.

Fertilization-->

Temperature-->{Enzymes,Hormones,Receptors}-->

Gonad determining genes-->

Gonad formation-->

Hormones-->

Sexual differentiation of phenotype

***

NO SEX CHROMOSOMES, but do have genes that play a role in sex determination.

100% females produced at lower temperatures --> 90% males at ~31.5 degrees --> back to 95% females at 35 degrees.

Males less attracted to females produced at higher temperatures - temp also affects phenotypic behavior.

Embryos at male-producing temperatures treated with E2 --> 100% females.

Embryos at female-producing temperatures treated with T had no affect.

Embryos at male-producing temps treated with T

Sex steroids play a role...just don't know what.

1. EXOCRINE - Seminal fluid - doesn't make all of it...prostate and seminal vesicles also do

2. ENDOCRINE - Androgens and peptides, like inhibin

3. GAMETOGENIC

1. GAMETES= mature sperm

2. LEYDIG CELLS (INTERSTITIAL CELLS) - just outside the BASEMENT MEMBRANE (aka BASAL LAMINA)

3. SERTOLI CELLS (SUSTENTACULAR CELLS) - surround sperm - "nursing" cells

Spermatagonium (2n)-->

Primary spermatocyte (2n)-->(meiotic division 1)-->

Secondary spermatocyte (n)-->(meitoic division 2)-->

Spermatid (n) =(immature sperm)

SEMINIFEROUS TUBULE

EPIDIDYMIS

VAS DEFERENS

EJACULATORY DUCT

Nothing

URETHRA

PENIS

RETE TESTIS which has tubules that feed into the epididymis

Epididymis feeds into the vas deferens (duct) which allows sperm to exit the body

Spermatogenesis:

LH receptors found...and stimulates...

FSH receptors found...and stimulates...

LHRs on LEYDIG CELLS and stimultaes ANDROGEN PRODUCTION

FSHRs on SERTOLI CELLS and stimulates production of ANDROGEN BINDING PROTEINS and promotes SPERMATOGENESIS

1. FOLLICULAR PHASE - oocyte develops inside follicle

2. OVULATION - follicle ruptures and oocyte released into fallopian tube

3. LUTEAL PHASE - ovulated follicle forms the corpus luteum

About how many oocytes does a female have at:

~20wks of gestation?

at birth?

puberty?

How many times will she ovulate in her lifetime?

What is utresia?

~20wks of gestation: 6-7 MILLION PRIMARY OOCYTES - most oocytes she will every have (arrested in prophase I)

At birth: ~2 MILLION PRIMARY OOCYTES

Puberty: ~100,000-400,000 PRIMARY OOCYTES

Female ovulates ~500 times

Utresia= DEATH OF OOCYTES

Primary oocyte arrested in ______ until....

Another name for the secondary oocyte...

Primary oocyte arrested in PROPHASE I until LH INDUCES FUTHER MATURATION

GRAAFIAN FOLLICLE

***

6-12 follicles enter final maturation, but only one follicle fully matures - this is the one that is most sensitive to FSH.

This follicle also secretes inhibitors that cause other non-mature follicles to undergo utresia.

Primary oocyte is __% of max growth.

How long does it take for a primary oocyte to become a secondary oocyte?

Primary oocyte is 50% of max growth.

Takes ~300 DAYS to become secondary oocyte.

Glycoprotein membrane surrounding the plasma membrane of the oocyte.

What surrounds this membrane?

ZONA PELLUCIDA

...surrounded by GRANULOSA CELLS

ZONA PELLUCIDA - glycoprotein membrane surrounding the plasma membrane of the oocyte

GRANULOSA CELLS - cell layer containing FSH receptors and aromatases to convert androgens to estradiol

THECA INTERNA - contains receptors for LH and produce androstenedione

THECA EXTERNA - contain abundant collagen and are mainly supportive

If no pregnancy, corpus luteum REGRESS after 9-10 days.

If there IS pregnancy, the corpus luteum is maintained until the end of the FIRST TRIMESTER.

What is the Hemorrhagicum?

What is the Corpus Albicans?

Hemorrhagicum= 'BLOODY BODY' = TEMPORARY STRUCTURE FORMED RIGHT AFTER OVULATION...heals to become the corpus luteum

Corpus Albicans= REGRESSED CORPUS LUTEUM

What is E2's effect on gonadotropins during the

Follicular phase?

Ovulation?

Luteal phase (aka Secretory phase)?

Follicular phase - INHIBITION OF LH AND FSH

Ovulation - STIMULATION OF LH AND FSH

Luteal phase - INHIBITION OF LH AND FSH

E2 promotes BUILDING of the endometrium during the FOLLICULAR PHASE

P4 MAINTAINS the endometrium during the LUTEAL PHASE

***

E2 increases during luteal phase from developing follicles

1. INHIBITING LH so that another cycle doesn't start

2. STIMULATING UTERUS to prepare it for implantation of the egg

PROESTRUS - just before ovulatin - RISE IN E2 and LH SURGE - E2 promotes production of P4 RECEPTORS IN THE BRAIN (priming)

ESTRUS - just after ovulation - RISE IN P4 (like menstrual cycle) - sexually receptive

DIESTRUS - corpus luteum activity

What is Luteolysis?

What causes it?

REGRESSION OF CORPUS LUTEUM

In DOMESTIC ANIMALS, luteolysis caused by PROSTAGLANDIN F2α (PGF2α) - Produced by the uterus.

Uterine vein runs by ovarian blood supply which is how PGF2α is taken up into ovaries.

In PRIMATES, luteolysis caued by ESTRONE - a luteolytic estrogen produced by the corpus luteum.

***

PGF2α AKA LUTALASE or LUTEOLYSIN

P4 which is high during luteal phase promotes production of PGF2α.

...if pregnancy occurs, something inhibits PGF2α, but don't know what it is.

***

Exploited in artifical insemination of livestock.

Injection of PGF2α puts animals all on same cycle so in heat at the same time.

What is vitellogenesis?

Is it cyclical?

What stimulates vitellogenin production?

Vitellogenesis is the period of yolk production.

It is cyclical only insofar as ovulation induces another cycle.

Vitellogenin production stimulated by E2.

Male deposits sperm into female oviduct called the spermatheca where it stays for several months until female finishes yolk production which is when she will ovulate...most species yolk up eggs during copulation and ovulate months later.

***

Vitellogenesis ONLY in females, except for males exposed to E2.