kuliah endokrinologi

ENDOKRINOLOGIREPRODUKSI

Bayu Kurniawan, drBayu Kurniawan, dr..

Topik PembelajaranTopik Pembelajaran

• Dasar Endokrinologi Reproduksi Dasar Endokrinologi Reproduksi WanitaWanita

• Dasar Endokrinologi Reproduksi PriaDasar Endokrinologi Reproduksi Pria

Dasar Dasar Endokrinologi Endokrinologi

Reproduksi Reproduksi WanitaWanita

Tujuan PembelajaranTujuan Pembelajaran

Mahasiswa mampu memahami & Mahasiswa mampu memahami & menjelaskan :menjelaskan : Fenotip wanitaFenotip wanita Sistem endokrin & reproduksi Sistem endokrin & reproduksi Konsep MenstruasiKonsep Menstruasi

THE FEMALE - PHENOTYPE

What makes a woman ?

1. Chromosomal composition of female is XX

2. Gonads that are functionally and structurally ovaries

3. Female sex hormone production

4. Appropriate internal and external genitalia

5. Self - Acceptance of female role

Endocrine SystemEndocrine System

• Communication systemCommunication system– Allows for cells in distant parts of body Allows for cells in distant parts of body

to communicateto communicate– Communication generally slower in Communication generally slower in

onset, but longer in duration, compared onset, but longer in duration, compared to nervous system communicationto nervous system communication

• Consists of all the organs that Consists of all the organs that secrete hormones (endocrine secrete hormones (endocrine organs) organs)

HormonesHormones

Chemical MessengersChemical Messengers Produced by an endocrine glandProduced by an endocrine gland Released into and carried via bloodstream Released into and carried via bloodstream

to target tissuesto target tissues Target tissues = tissues bearing receptors that Target tissues = tissues bearing receptors that

can bind and physiologically respond to the can bind and physiologically respond to the chemical messenger in questionchemical messenger in question

Amount of chemical messenger produced and Amount of chemical messenger produced and released intocirculation is generally released intocirculation is generally very smallvery small

SEX HORMONES - FEMALESEX HORMONES - FEMALE

1. Gonadotrophin-releasing hormone (GnRH) (decapeptide) LH Releasing Factor, FSH Releasing Factor

2. Luteinising hormones (LH)

3. Follicle stimulating hormone (FSH) 4. Inhibin (Protein hormone)

5. Activin (Protein hormone)

6. estrogens, progesterons & androgens

Peptides

Steroids

Hormones responsible for development and maintenance of female phenotype:

TRADITIONAL ENDOCRINE SYSTEMTRADITIONAL ENDOCRINE SYSTEM

second messengersnucleus

cellular effects

biological response

general blood circulation

capillary

Feedback loop

A B

stimulus

nucleushormone

Hormone producing cell

second messengersCa2+

Norman, A.W.; Litwack, G. (1997) Hormones 2nd Ed. Academic Press

Target Cell

hormone

Reproductive SystemReproductive System

• Survival of the organismSurvival of the organism– Other systems of the body work together Other systems of the body work together

to maintain homeostasis and promote to maintain homeostasis and promote survival of the organism under varying survival of the organism under varying environmental conditionsenvironmental conditions

• Survival of the speciesSurvival of the species– Reproductive system is designed to Reproductive system is designed to

package and transmit genetic information package and transmit genetic information from generation to generation, therefore from generation to generation, therefore promotes survival of the species over timepromotes survival of the species over time

Major Functions of Male and Major Functions of Male and Female Reproductive SystemsFemale Reproductive Systems

Production of gametesProduction of gametes Male gametes = spermMale gametes = sperm

Spermatogenesis = production of mature Spermatogenesis = production of mature spermsperm

Female gametes = eggs (ova)Female gametes = eggs (ova) Oogenesis = production of mature eggsOogenesis = production of mature eggs

SteroidogenesisSteroidogenesis Production of steroid hormonesProduction of steroid hormones

estrogens, progesterons, androgensestrogens, progesterons, androgens

PEPTIDE/ PROTEIN HORMONES INVOLVED IN PEPTIDE/ PROTEIN HORMONES INVOLVED IN FEMALE DEVELOPMENT AND REPRODUCTIONFEMALE DEVELOPMENT AND REPRODUCTION

Hormone Site of Principal target tissue Biological function Production

GnRH Hypothalmus Adenohypophysis Stimulation of release of FSH and LH

FSH Adenohypo- Ovarian Granulosa Growth ovarian follicle physis and thecal cells Stimulation estrogen

production

LH Adenohypo- Corpus luteum Stimulate progesterone physis production

Inhibin Follicle granulosa Hypothalmus- Participate in feedback cell pituitary inhibition of FSH

secretion

Activin Follicle granulosa Hypothalmus Increase secretion of FSH

Female Reproductive Female Reproductive System (1)System (1)

• Fase IntrauterineFase Intrauterine

• Fase BayiFase Bayi

• Fase AnakFase Anak

• Fase Pra-pubertasFase Pra-pubertas

• Fase ReproduksiFase Reproduksi

• Fase KlimakteriumFase Klimakterium

• Fase SeniumFase Senium

Female Reproductive Female Reproductive System (2)System (2)

• Poros Hormon ReproduksiPoros Hormon Reproduksi- Susunan Sentral - Susunan Sentral

- Pineal- Pineal- Hipotalamus- Hipotalamus- Hipofise- Hipofise

- Susunan Perifer- Susunan Perifer- Ovarium- Ovarium- Endometrium- Endometrium

• Organ Endokrin Ekstra GonadOrgan Endokrin Ekstra Gonad- Timus- Timus- Tiroid- Tiroid- Adrenal - Adrenal - Pankreas- Pankreas

PINEAL (1)PINEAL (1)

•Kelenjar kecil di posterior Kelenjar kecil di posterior hipotalamushipotalamus

•Embriologis berasal dari Embriologis berasal dari diensefalon posteriordiensefalon posterior

•Organ sisa ?Organ sisa ?


•SintesisSintesis Melatonin (>> aktif)Melatonin (>> aktif) 5-Metoksi-Triptofol5-Metoksi-Triptofol Arginin VasotosinArginin Vasotosin

•SekresiSekresi Belum seluruhnya diketahuiBelum seluruhnya diketahui Irama Sirkadian, Pulsatil Irama Sirkadian, Pulsatil

(Melatonin)(Melatonin)


FungsiFungsi Belum seluruhnya diketahuiBelum seluruhnya diketahui Dipengaruhi cahaya & hormonDipengaruhi cahaya & hormon Terdapat reseptor hormon steroid seks & Terdapat reseptor hormon steroid seks &

prolaktinprolaktin Berpengaruh terhadap :Berpengaruh terhadap :

- Poros hipotalamus-hipofise-gonad- Poros hipotalamus-hipofise-gonad- Reproduksi- Reproduksi- Siklus Seksual & Siklus haid- Siklus Seksual & Siklus haid- Seks Sekunder- Seks Sekunder- Genitalia Interna- Genitalia Interna- Ovulasi- Ovulasi

Hypothalamic-Pituitary AxisHypothalamic-Pituitary Axis HypothalamusHypothalamus

• Region of brain (diencephalon) Region of brain (diencephalon) • Lies below third ventricle at base of Lies below third ventricle at base of

brainbrain• Important regulator of endocrine Important regulator of endocrine

actionaction Pituitary Gland (hypophysis)Pituitary Gland (hypophysis)

• Endocrine gland connected to Endocrine gland connected to hypothalamus by infundibulum hypothalamus by infundibulum (stalk containing nerves and small (stalk containing nerves and small blood vessels)blood vessels)

Hypothalamus (1)Hypothalamus (1)• Contains neuroendocrine cells that Contains neuroendocrine cells that

release neurohormones which release neurohormones which 1. enter the portal vessels and are 1. enter the portal vessels and are

transported to anterior pituitarytransported to anterior pituitary

2. regulate anterior pituitary hormone 2. regulate anterior pituitary hormone productionproduction

• Contains neuroendocrine cells whoseContains neuroendocrine cells whose– cell bodies lie within hypothalamuscell bodies lie within hypothalamus

• Hypothalamus = site of hormone productionHypothalamus = site of hormone production

– axons travel through hypothalamic-axons travel through hypothalamic-pituitary stalk and terminate in posterior pituitary stalk and terminate in posterior pituitarypituitary• Posterior pituitary = site of hormone storage Posterior pituitary = site of hormone storage

and releaseand release

Hypothalamus (2)Hypothalamus (2)

Hypothalamus Hormones Hypothalamus Hormones

Hypothalamic Releasing Hypothalamic Releasing HormonesHormones

Hypothalamic Inhibitory Hypothalamic Inhibitory HormonesHormones


• Produced in and released from Produced in and released from hypothalamushypothalamus

• Enter portal blood vessels and Enter portal blood vessels and are transported to ANTERIOR are transported to ANTERIOR PITUITARYPITUITARY

• Stimulate discrete cell types Stimulate discrete cell types within anterior pituitary to within anterior pituitary to secrete additional hormone(s) secrete additional hormone(s)


• Corticotropin Releasing Hormone Corticotropin Releasing Hormone (CRH)(CRH)– Acts on corticotrophsActs on corticotrophs– Stimulates AP production of Stimulates AP production of

adrenocorticotropic hormone (ACTH)adrenocorticotropic hormone (ACTH)

• Thyrotropin Releasing Hormone (TRH)Thyrotropin Releasing Hormone (TRH)– Acts on thyrotrophs Acts on thyrotrophs – Stimulates AP production of Thyroid Stimulates AP production of Thyroid

Stimulating Hormone (TSH)Stimulating Hormone (TSH)


• Gonadotropin Releasing Gonadotropin Releasing Hormone (GnRH) Hormone (GnRH) – Previously known as Luteinizing Previously known as Luteinizing

Hormone Releasing Hormone Hormone Releasing Hormone (LHRH)(LHRH)

– Acts on lactotrophs to stimulate AP Acts on lactotrophs to stimulate AP production of Follicle-Stimulating production of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (FSH) and Luteinizing Hormone (LH)Hormone (LH)

Hypothalamic Releasing Hypothalamic Releasing & Inhibitory Hormones& Inhibitory Hormones

• Growth Hormone Releasing Hormone Growth Hormone Releasing Hormone (GHRH = somatotropin)(GHRH = somatotropin)– Acts on somatotrophsActs on somatotrophs– Stimulates AP production of Growth Stimulates AP production of Growth

Hormone (GH)Hormone (GH)• Growth Hormone Inhibitory Hormone Growth Hormone Inhibitory Hormone

(GIH = somatostatin)(GIH = somatostatin)– Acts on somatotrophsActs on somatotrophs– Inhibits AP production of Growth Inhibits AP production of Growth

HormoneHormone

Pituitary GlandIn humans has two lobes = distinct glands

• Anterior (toward front of head) lobe = adenohypophysis

• Posterior (toward back of head) lobe = neurohypophysis

Lobes connected to hypothalamus by different means• Anterior lobe connected by (portal) blood

vessels• Posterior lobe connected by nerves (axons)

Anterior Pituitary (AP)

Endocrine (hormone-secreting) gland containing several different cells types Lactotrophs; secrete prolactin Gonadotrophs; secrete LH and FSH Somatotrophs; secrete Growth hormone Thyrotrophs; secrete Thyroid stimulating hormone Corticotrophs; secrete Adrenocorticotropic

Hormone

Connected to hypothalamus by portal blood vessels

ProlaktinProlaktin

FungsiFungsi

o Merangsang Merangsang galaktopoeisis galaktopoeisis (mempertahankan laktasi & (mempertahankan laktasi & laktogenesis untuk membentuk laktogenesis untuk membentuk

air susu)air susu)

o Memicu mammogenesisMemicu mammogenesis

FSH & LHFSH & LH

Fungsi Fungsi

- Pematangan folikel- Pematangan folikel

- Ovulasi- Ovulasi

- Pembentukan korpus luteum- Pembentukan korpus luteum

- Sintesis steroid seks- Sintesis steroid seks

Posterior Pituitary

Outgrowth of the hypothalamus; composed of neural tissue

Specific neuroendocrine cells in hypothalamus have axons that project through the stalk and into the posterior pituitary

Secretes two important hormones Oxytocin (OXY) Antidiuretic hormone (ADH)

Fungsi Oxytocin Persalinan : kontraksi uterus Pengeluaran air susu dgn kontraksi

mioepitel payudara

Fungsi ADH Mengendalikan osmolalitas & volume

plasma

OvariumOvarium Fungsi Utama Fungsi Utama

1. 1. Fungsi ProliferatifFungsi Proliferatif

Sumber ovum selama fase Sumber ovum selama fase reproduksireproduksi

2. Fungsi Sekretorik2. Fungsi Sekretorik

Pembentukan & pengeluaran Pembentukan & pengeluaran hormon hormon steroid seks (estrogen, steroid seks (estrogen, progesteron & progesteron & androgen)androgen)

Estrogen (1)Estrogen (1)

• Hormon steroid dgn 10 atom C, Hormon steroid dgn 10 atom C, dibentuk dari 17-ketosteroid dibentuk dari 17-ketosteroid androstendionandrostendion

• Estrogen alamiah : estradiol (E2), estron Estrogen alamiah : estradiol (E2), estron (E1), estriol (E3) E2:E1:E3 = 10:5:1(E1), estriol (E3) E2:E1:E3 = 10:5:1

• Disintesis di ovarium, adrenal, plasenta, Disintesis di ovarium, adrenal, plasenta, testis, jaringan lemak, SSPtestis, jaringan lemak, SSP


• Khasiat UmumKhasiat Umum

- Merangsang sintesis DNA melalui - Merangsang sintesis DNA melalui RNARNA

- Membentuk messenger RNA- Membentuk messenger RNA

Meningkatkan sintesa proteinMeningkatkan sintesa protein

Estrogen (3)Estrogen (3)• Khasiat KhususKhasiat Khusus

- Endometrium : - Endometrium : memicu proliferasi memicu proliferasi endometrium, endometrium, memperkuat memperkuat kontraksi uteruskontraksi uterus- Serviks : mengubah konsentrasi getah serviks - Serviks : mengubah konsentrasi getah serviks saat saat ovulasiovulasi- Vagina : - Vagina : perubahan selaput vagina, perubahan selaput vagina, meningkatkan meningkatkan produksi getah, produksi getah, meningkatkan kadar meningkatkan kadar glikogen, glikogen, peningkatan produksi asam laktat, peningkatan produksi asam laktat, memperkecil kemungkinan infeksimemperkecil kemungkinan infeksi- Ovarium : memicu sintesis reseptor FSH & LH, - Ovarium : memicu sintesis reseptor FSH & LH,

mengatur kecepatan keluarnya mengatur kecepatan keluarnya ovum, ovum, mempersiapkan mempersiapkan spermatozoaspermatozoa


Others:

• Increase clotting factors in the blood

•Decrease rate of bone resorption

• Increase sodium and water retention

•Mood & behavior

•Spermatogenesis

• Increase HDL and decrease LDL

Progesteron (1)Progesteron (1)

Hormon steroid dgn 21 atom CHormon steroid dgn 21 atom C Dibentuk di folikel, plasenta & adrenalDibentuk di folikel, plasenta & adrenal Khasiat Umum Khasiat Umum

Mempersiapkan tubuh untuk kehamilanMempersiapkan tubuh untuk kehamilan(syarat mutlak konsepsi & implantasi)(syarat mutlak konsepsi & implantasi)

Terjadi karena pengaruh estradiol, Terjadi karena pengaruh estradiol, karena estradiol mensintesis reseptor karena estradiol mensintesis reseptor progesteronprogesteron

Progesteron (2)Progesteron (2)

Khasiat KhususKhasiat Khusus- Endometrium : perubahan sekretorik - Endometrium : perubahan sekretorik

(fase luteal)(fase luteal)- Serviks : barier terhadap spermatozoa - Serviks : barier terhadap spermatozoa (fase luteal)(fase luteal)- Miometrium : menurunkan tonus miometrium- Miometrium : menurunkan tonus miometrium- Suhu Basal Badan : peningkatan suhu basal - Suhu Basal Badan : peningkatan suhu basal

badan segera setelah badan segera setelah ovulasi (termogenik) ovulasi (termogenik)

Androgens: Physiological & Pharmacological Actions

Necessary for development of male fetus

Responsible for major changes that occur in males at puberty

Anabolic actions Maintains sexual function in

males Participates in pubertal growth

spurt & hair growth in females

EndometriumEndometrium

•FungsiFungsio NidasiNidasio MenstruasiMenstruasio Petunjuk gangguan Petunjuk gangguan

fungsional fungsional & steroid seks& steroid seks

Organ Endokrin Ekstra GonadOrgan Endokrin Ekstra Gonad

ThymusThymus

ThyroidThyroid

AdrenalAdrenal

PankreasPankreas

THYMUSTHYMUS

Berubah mengikuti usia Berubah mengikuti usia Tumbuh kembangTumbuh kembang Puncak sesaat sebelum Puncak sesaat sebelum

pubertaspubertas Aktivasi Aktivasi Hypothalamic- Hypothalamic-

Pituitary AxisPituitary Axis Terdapat reseptor estrogen & Terdapat reseptor estrogen &

androgenandrogen

THYMUSTHYMUS•Sekresi & FungsiSekresi & Fungsi

- - Timosin a-1 & Timosin Timosin a-1 & Timosin ββ-4-4 Aktivasi sekresi LH-RH Aktivasi sekresi LH-RH HipotalamusHipotalamus

Sekresi kortikosteroidSekresi kortikosteroid

- - Didapatkan Oksitosin & Didapatkan Oksitosin & Vasopresin Vasopresin

Fungsi ???Fungsi ??? ParakrinParakrin

THYROID• Sekresi Hormon Thyroxin• Gangguan sekresi : Hipertiroid –

Hipotiroid• Hipertiroid

- Gangguan silkus haid (ringan)• Hipotiroid

- Gangguan fertilitas (gangguan siklus haid berat sd

anovulasi)- Galaktorea

Hipotiroid

• T3 & T4 rendah• TRH tinggi• PRL tinggi• PRL hambat FSH & LH• Tingkatkan kadar androgen• Hambat pematangan folikel

AdrenalAdrenal

• Produksi androgen wanita : ovarium & Produksi androgen wanita : ovarium & adrenal adrenal >>> >>> berlebihanberlebihan >>> Ggn. Reproduksi >>> Ggn. Reproduksi

• Intake kalori Intake kalori +++ >>> +++ >>> aktivitas aktivitas adrenaladrenalmeningkatmeningkat

• Androgen +++ >>> Ggn. GonadostatAndrogen +++ >>> Ggn. Gonadostat hipotalamus-hipofise >> Ggn. Hypothalamic-hipotalamus-hipofise >> Ggn. Hypothalamic-

Pituitary Axis >>Resistensi folikel ovariumPituitary Axis >>Resistensi folikel ovarium

PankreasPankreas

• Sekresi InsulinSekresi Insulin• Normal: Insulin merangsang FSH – LH (Hipofise)Normal: Insulin merangsang FSH – LH (Hipofise)• Fungsi : Fungsi :

- meningkatnya sintesis estrogen & progesteron- meningkatnya sintesis estrogen & progesteron- sintesis & sekresi proteoglikan & - sintesis & sekresi proteoglikan & aktivator plasminogenaktivator plasminogen- timbulnya reseptor LH & Prolaktin- timbulnya reseptor LH & Prolaktin

• Kadar Insulin ~ Kadar androgen (androstendion Kadar Insulin ~ Kadar androgen (androstendion & testosteron) & testosteron)

• Obesitas – Anovulasi - Hirsutisme Obesitas – Anovulasi - Hirsutisme

PROSTAGLANDINPROSTAGLANDIN

• OvulasiOvulasiMemicu pecahnya folikel dg mempengaruhi vaskuler & Memicu pecahnya folikel dg mempengaruhi vaskuler & kontraksi ovariumkontraksi ovarium

• SpermatozoaSpermatozoaPG dari spermatozoa >> kontraksi & relaksasi uterus – tubaPG dari spermatozoa >> kontraksi & relaksasi uterus – tuba

• MenstruasiMenstruasiMerangsang otot polosMerangsang otot polos

• DismenoreaDismenoreaHiperkontraktilitas uterus (kadar progesteron Hiperkontraktilitas uterus (kadar progesteron rendah)rendah)

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