Reproduction 2

MCB 136
Lecture 31
guest lecturer: Marla Feller
mfeller@berkeley.edu

Chapter 17 — many figures from Chapter….

 Review from last lecture
1. Genetics: Males possess one X and one Y chromosome. Females have two
X chromosomes

2. Y-chromosome contains the SRY gene, which encodes for a protein that
triggers the development of the testes. In the presence of SRY, signaling leads
to the development of the Wolfferian duct and the regression of the Mullerian
duct.
— Mullerian duct —> internal female genitalia
— Wollffian duct —> internal male genitalia
(pages 590-591, Figure 17-3)

3. Hormones: Testosterone and DHT are male sex hormones, while Estrogen
and Progesterone are female sex hormones.

4. Fertilization requires motile hyperactivated spermatozoa and fertilization

occurs in ampulla of the Fallopian tube.
 Outline for today’s lecture

1. Basic organization of hormone signaling that controls the

release of sex hormones

2. Hormone signaling in males: testosterone

3. Hormone signaling in females: estrogen/progesterone and

the ovarian cycle
 Differences between male and female primary
reproductive organs (gonads)

Males Females

gonads Testes Ovaries

Function 1:
spermatozoan ova: eggs
gametogenesis

Function 2:
estrogen/
secretion of testosterone
progesterone
hormones
 Endocrine signaling and feedback loops in
reproductive control

Hormones: chemical messengers that

are secreted from cells into blood
(endocrine) or into the nearby tissue
(paracrine).

Secreting cells located in various organs

throughout the body - e.g. hypothalamus,
pituitary gland, gonads)

Target: Any cell that has a receptor,

including another endocrine cells

Gonads: primary reproductive organs

Sex Hormones: secreted from gonads,

e.g. testosterone and DHT (male) or
estrogen and progesterone (female)
Figure 17-1
Negative feedback vs positive feedback loops

Secreting cells

Hormone 1

Target tissue
(receptor for
Hormone 1)

Hormone 2
Negative feedback vs positive feedback loops

Stimulation of target tissue —

Secreting cells increasing levels of hormone 1 lead to
increases in hormone 2

Hormone 1
+
Target tissue
(receptor for
Hormone 1)

Hormone 2
Negative feedback vs positive feedback loops

Stimulation of target tissue —

Secreting cells increasing levels of hormone 1 lead to
increases in hormone 2

Hormone 1
Inhibition of target tissue —increasing
- levels of hormone 1 lead to decreases in
hormone 2
Target tissue
(receptor for
Hormone 1)

Hormone 2
Negative feedback vs positive feedback loops

Stimulation of target tissue —

Secreting cells increasing levels of hormone 1 lead to
increases in hormone 2
Hormone 1
Inhibition of target tissue —increasing
levels of hormone 1 lead to decreases in
hormone 2
Target tissue
(receptor for
Hormone 1) Feedback - Hormone 2 binds to
secreting cells

Hormone 2
Negative feedback vs positive feedback loops

+ Stimulation of target tissue —

Secreting cells increasing levels of hormone 1 lead to
increases in hormone 2
Hormone 1
Inhibition of target tissue —increasing
levels of hormone 1 lead to decreases in
hormone 2
Target tissue
(receptor for
Hormone 1) Feedback - Hormone 2 binds to
secreting cells

Hormone 2 Positive feedback - hormone 2 stimulates

release of hormone 1
Negative feedback vs positive feedback loops

- Stimulation of target tissue —

Secreting cells increasing levels of hormone 1 lead to
increases in hormone 2
Hormone 1
Inhibition of target tissue —increasing
levels of hormone 1 lead to decreases in
hormone 2
Target tissue
(receptor for
Hormone 1) Feedback - Hormone 2 binds to
secreting cells

Hormone 2 Positive feedback - hormone 2 stimulates

release of hormone 1

Negative feedback - hormone 2 inhibits

release of hormone 1
 Hormone signaling and feedback loops in males

Hypothalamus is in the brain

gonadotropin-releasing hormone

anterior pituitary is in the brain

follicle-stimulating hormone and

luteinizing hormone (same in male and
females)
Gonads = testes in males.
Sertoli cells: Leydig cells:
receptors for receptors for
FSH LH

inhibin testosterone

Figure 17-12
 Implications of these feedback loops in men

1. Testosterone inhibits generation of LH via negative

feedback on hypothalamus AND negative feedback
on anterior pituitary.
2. Negative feedback loops keep hormone levels fairly
constant throughout the day. Hence continuous
sperm production

(aside: Testosterone follows a circadian cycle - highest in the

morning)
 ml; P < 0.001, by unpaired t test). Similarly, the ampli- is perform
tude of the circadian rhythms determined by cosinor likely to a
Real
analysis was data: Circadian
significantly rhythm
greater in the of
young men obtained
(mean ± SEM, 1.64 ± 0.18 ng/ml) than in the old men
testosterone levels in young vs. old men differ betw
Two ve
8-1
Bremner et al 1983
obtained
strate a d
and old m
and FSH
r*» YOUNG MEN
younger
23-28 years old o
ness to hC
6-
Those fin
in testicul
that these
basal test
frequent
58-82 years old
each man
0800 1200 1600 2000 2400 0400 0800 related ch
CLOCK TIME (HOURS) that the s
FIG. 1. Hourly serum testosterone levels (mean ± SEM) in normal experimen
young (n = 17) and old (n = 12) men. Blood samples were obtained circadian
Implications of these feedback loops in men

1. Testosterone inhibits generation of LH via negative

feedback on hypothalamus AND negative feedback
on anterior pituitary.
2. Negative feedback loops keep hormone levels fairly
constant throughout the day. Hence continuous
sperm production (aside: Testosterone follows a
circadian cycle - highest in the morning)
3. Negative feedback loops must be taken into account
when thinking about dysfunction. Test yourself on
Figure 17-12 Physiological Inquiry in book
example: Anterior pituitary dysfunction -> low sperm count

Solution 1. give testosterone alone?

— NO

Solution 2. give testosterone + LH +

FSH — BETTER
 Effects of testosterone on physiology
Target Effect
Sertoli cells Generation of sperm

Hypothalamus Decreases GnRH secretion

anterior pituitary Inhibits LH secretion

Conversion to DHT Induces differentiation of external

male reproductive organs
Bone Stimulates growth

A few targets in brain increases sex drive and (might)

increase aggressive behavior
Kidneys Increase red blood cells production
 Endocrine signaling and feedback loops in
reproductive control — females

GnRH; FSH and LH same as males

Gonads: Ovaries

Sex Hormones: estrogen,

progesterone, inhibin

Target: Any cell that has a receptor,

Figure 17-1
including another endocrine cells
 Hormone signaling and feedback loops in females

Hypothalamus is in the brain

gonadotropin-releasing hormone

anterior pituitary is in the brain

follicle-stimulating hormone and

luteinizing hormone

Gonads = ovaries in females.

follicles
Theca cells:
Granulosa cells:
receptors for
receptors for FSH
LH

Estrogen
progesterones
Figure 17-21 inhibin
 In females: gonad function is cyclical

Summary of ovarian events

follicle = structure that contains an ovum and secretes hormones, contains granules and theca cells
ovulation = expulsion of mature ovum from dominant follicle
corpus luteum = derived from follicle/secretes hormones
 Summary of ovarian events

Fig 17.18
Plasma hormone concentrations
Plasma hormone concentrations
 Hormone signaling and feedback loops in early to
mid follicular phase
Hypothalamus is in the brain

gonadotropin-releasing hormone

anterior pituitary is in the brain

follicle-stimulating hormone and

luteinizing hormone

Gonads = ovaries in females.

follicles
Theca cells:
Granulosa cells:
receptors for
receptors for FSH
LH

Estrogen
inhibin
Figure 17-21
 Hormone signaling and feedback loops in late
follicular phase
Hypothalamus is in the brain

gonadotropin-releasing hormone

anterior pituitary is in the brain

follicle-stimulating hormone and

luteinizing hormone

Dominant
follicle

Estrogen

Figure 17-21 LH surge triggers ovulation and formation of corpus luteum

Hormone signaling and feedback loops in luteal phase

Hypothalamus is in the brain

gonadotropin-releasing hormone

anterior pituitary is in the brain

follicle-stimulating hormone and

luteinizing hormone

Corpus luteum

Progesterone
Estrogen
Real data: Pulsatile
oscillation in LH for
women as they age

Apter et al, 1994

 Effects of estrogen
Target Effect

Hypothalamus Decreases GnRH secretion

anterior pituitary Inhibits LH secretion

Various targets in growth and development, e.g. uterus

reproductive tract

Bone Stimulates growth

Lipid Increase HDL (good cholesterol )and

decrease LDL (bad cholesterol)
Summary - reproductive physiology

• Release of sex hormones is controlled by a chain

hormones that initiates in the brain.

• Testosterone is produced and released from a

particular cell class in testes called Leydig cells

• Estrogen is produced and released from granules

cells, progesterone released from corpus luteum.
Follows ovarian cycle

• Sex hormones have impacts both in maturation and

function of reproduction system and on other
physiological systems, e.g bone