1. The hypothalamus involvement in
sexual dimorphism
Presented by: Maria Hajje
Supervised by: Dr. Pauline Aad
Course: Bio 485
Fall 2013©

2. Introduction
Sexual dimorphism is
determined by signs of
differentiation between male or
female

3. Sexual Differentiation
External
Genitalia
Internal reproductive
system
Brain
Secondary sexual
dimorphism
Neo-natal
Post-natal at
puberty

4. Secondary sexual dimorphism – Postnatal
http://www.livescience.com/33513-men-vs-women-our-physical-differences-
explained.html

5. Timing of the embryogenic development
and dimorphism
http://www.nap.edu/openbook.php?record_id=4797&pag

6. Embryonic sexual dimorphism
Males
-Wolffian Ducts
-Testes
-Penis and Scrotum
-Main Hormone 
testosterone
Females
-Mullerian Ducts
-Ovaries
-Uterus, Vagina and clitoris
-Main Hormone estrogen
Human Reproductive Biology, Third Edition, Sylvia S. Mader, P. 79

7. The major pathways of male and female
sexual differentiation. TDF, testis-
determining factor
http://www.glowm.com/resources/glowm/cd/pages/v5/v5c07

8. Figure 1 Gene regulatory networks in embryonic gonadal development
Ono, M. & Harley, V. R. (2012) Disorders of sex development: new genes, new concepts
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2012.235
http://www.nature.com/nrendo/journal/v9/n2/fig_tab/nrendo.2012.235_F1.html

9. Determining factors of dimorphism
 Presence or absence of Y chromosome
 The type of hormones secreted
 The secretion of hormones is regulated by the
hypothalamus
Objective
 Observe the role of he hypothalamus in
sexual dimorphism

10. The hypothalamus
Functions of hypothalamus
Regulation of eating and drinking
Cardiac rhythm
Regulation of autonomic nervous
system
Emotional behavior
Regulation of reproductive
hormones and behavior

11. The sex hormones-postnatal
Human Reproductive Biology, Third Edition, Sylvia S. Mader, P. 82-83
FSH
Sperm.
LH  A4
A4 
2ndary 2ndary2ndary

12. Neo-natal dimorphic nuclei
The 4 interstitial nuclei and the dimorphic nuclei
Sexual dimorphic nucleus of
the pre-optic anterior
hypothalamus (SDN-POA)
Interstitial Nucleus of the
anterior hypothalamus
(I.N.A.H.)
Bed nucleus of the
stria terminalis
(BNST) – anterior
Is homoseksualiteit wel aangeboren?
Achtergrond maandag 8 november 2010 Dit is een publicatie van

13. The SDN-POA nucleus
The Sdn-poa Area In The Human Brain: A Comparative Morphometric
Study, Michel A. Hofman And Dick F. Swaab
Male
SDN-POA
is 2 to 3
times
larger
than
female
SDN-POA
Variation in size of the SDN-POA

14. The variation of SDN-POA with age
This change
will cause an
impairment in
the hormonal
regulation
The influence of gonadectomy, androgen exposure, or a gonadal graft in the neonatal rat on
the volume of the sexually dimorphic nucleus of the preoptic area, carol d. JACOBSON,
et all.
Decrease in SDN-POA cell number with age

15. Hormones and SDN-POA – Neonatal
The influence of gonadectomy, androgen exposure, or a gonadal graft in the neonatal rat on
the volume of the sexually dimorphic nucleus of the preoptic area, carol d. JACOBSON,
et all.
Sequence of experimental treatment
1 Intact Gx
2 Sham Gx Oil Gx
3 Gx + Ovarian Graft Graft removed
4 Gx + Testicular Graft Graft removed
5 Gx Oil Sham surgery
6 Gx 100 μg of TP Sham surgery
7 Gx 1 mg of TP Sham surgery
Day
s
1 2 45 60
surgery
Hormone or oil
additions
surgery
Separation of males
and females and
sacrifice

16. Hormones and SDN-POA – Neonatal
The influence of gonadectomy, androgen exposure, or a gonadal graft in the neonatal rat on
the volume of the sexually dimorphic nucleus of the preoptic area, carol d. JACOBSON,
et all.
Male Female

17. Estrogen and SDN-POA – Neonatal
http://www.rbej.com/content/1/1/35/figure/F1?highres=y

18. AFP and SDN-POA – Neonatal
http://www.nature.com/neuro/journal/v9/n2/fig_tab/nn0206-155_F1.html
Action of AFP in testosterone/estrogen regulation

19. Diethylstilbestrol – Postnatal
High volumes of DES can
alter the growth of the SDN-
POA in adult females
resulting a bigger SDN-POA
than control adult female
Treatment with low doses of
DES showed no alternation
in SDN-POA volume
The third ventricle narrows
http://www.ib.cnea.gov.ar

20. Apoptosis and SDN-POA – Postnatal
 In females we have a highly number of apoptotic cell in
females located in the medial pre-optic nucleus (MPN)
 This apoptosis is due to two proteins:
1- BAX: BCL2-Associated X Protein
2- BCL-2 : B-cell CLL/lymphoma 2
 It was found that high rate of caspase-3 was activated in
female brains rather than male brains

21. Other effectors in the dimorphism of the
SDN-POA - Postnatal
Somatostatin NELL-2
-It is responsible for somatic
growth.
-Found in both male and female
SDN
-Days 8 to 35 of postnatal life,
somatostation mRNA positive
cells are larger in males than
females. The maximum size is
attained at day 15 than we have a
decrease. In females we do not
have any decrease in the
expression but they are smaller
than males.
-Neuroprotective
-Epidermal growth factor
-When NELL-2 was blocked 
smaller volume of SDN-POA
was shown in treated males vs.
controlled

22. Gene expression and pathways in
hypothalamus
Sex-specific modulation of gene expression networks in murine
hypothalamus ,Khyobeni Mozhui, Lu Lu, William E. Armstrong and

23. Homosexuality
Evidence for a Biological Influence in Male Homosexuality, Two pieces of
evidence, a structure w-thin the human brain and a genetic link, point to a
biological component for male homosexuality by Simon LeVay and Dean
INAH-3 in homosexual male

24. Homosexuality and Genetics
Males Females
57% of identical twins
24% of fraternal twins
13% of brothers
Heritability  53%
50% of identical twins
16% of fraternal twins
13% of sisters
Heritability  52%
Evidence for a Biological Influence in Male Homosexuality, Two pieces of
evidence, a structure w-thin the human brain and a genetic link, point to a
biological component for male homosexuality by Simon LeVay and Dean

25. Homosexuality
Gay brains structured like those of the opposite sex by Andy Coghlan
Brain reaction after sexual visual arousal in homosexual and heterosexual patients

26. Brain Imaging
http://expanded--
Brain map locates landmarks for memory, vision, language and arousal
memory vision language arousal
Male
Female