Stress in Early Pregnancy:The Role of Endocrine Immune System and Management

Noor Pramono NoerpramanaFakultas Kedokteran Universitas Diponegoro

Actual Management in Complicated PregnancyFK. Universitas Sebelas Maret ,Surakarta 15 Juli 2012

1. Stress

2. Hypothalamus hormones

3. Pituitary anterior hormones

4. HPA

5. HPG

6. Thyroid hormones

7. ADH

8. Stress CRH (HPA), GnRH (HPG), TRH, GHRH

9. Desidual prolactin, circulation prolactin

10. Stress Th1, Th2, immune system

11. Pregnancy failure, fetal programming

12. Management stress in early pregnancy

Contents

Stres

• Stres : Proses adaptasi

• Stres : - Aksis hypothalamo-pituitary-adrenal

(HPA)

- Aksis hypothalamo-pituitary-gonadal

(HPG)

- Sistem imun

Hormones of the hypothalamus

Hormone Target cells in the anterior pituitary gland

Effect on the anterior pituitary gland

Growth hormone releasing hormone (GHRH)

Somatotrophs ↑ GH release

Growth hormone inhibiting hormone (GHIH also called somatostatin)

Somatotrophs and thyrotrophs

↓ GH and TSH release

Corticotrophin releasing hormone (CRH)

Corticotrophs ↑ ACTH release

Gonadotrophin releasing hormone (GnRH)

Gonadotrophs ↑ LH and FSH release

Thyrotrophin releasing hormone (TRH)

Thyrotrophs and lactotrophs

↑ TSH and prolactin release

Prolactin releasing factors (PRF) Lactotrophs ↑ Prolactin release

Dopamine (prolactin inhibiting hormone)

Lactotrophs ↓ Prolactin release

Hormone of the anterior pituitary

The hormone secreted by anterior pituitary are large peptides ( about 200 amino acid residues) or glycopeptides

The six main hormones are– Growth hormone (GH)– Thyroid stimulating hormone (TSH also called

thyrotrophin).– Adrenocorticotrophic hormone (ACTH)– Luteinizing hormone (LH)– Follicle stimulating hormone (FSH)– Prolactin (PRL)

Hormones of the anterior pituitary gland

Hormone Synthesized by Stimulated by Inhibited by Target organ Effect

GH Somatotrophs GHRH GHIH and IGF-1 Liver Stimulates IGF-1 production and opposes insulin

TSH Thyrotrophs TRH T3 Thyroid gland Stimulates thyroxine release

ACTH Corticotrophs CRH Glucocorticoids Adrenal cortex Stimulates glucocorticoid and androgen release

LH+FSH Gonadotrophs GnRH, sex steroids

Prolactin, sex steroids

Reproductive organs

Release of sex steroids

Prolactin Lactotrophs PRF and TRH Dopamine Mammary glands and reproductive organs

Promotes growth of these organs and initiates lactation

MSH Corticotrophs - - Melanocytes in skin

Stimulates melanin synthesis

Beta-endorphin

Corticotrophs - - Unknown May be involved in pain control

Hormones of the anterior pituitary gland and their receptive target organs

HPA : Hormonal regulation of cortisol. (ACTH, adrenocorticotropic

hormone; CRH, corticotrophin releasing hormone)

HPG : Regulasi hormon FSH , LH, Prolaktin, Estrogen, Progesterone

Hormonal regulation of the thyroid hormones. (T3, Tri- iodothyronine; T4,thyroxine;TRH,thyrotrophin;releasing hormone; TSH, thyroid stimulating

hormone

prolactin

Hormonal regulation of plasma osmolarity by antidiuretic hormone (ADH)

Hormonal regulation of growth hormone

HPAHypothalamusCRH

ACTH

AdrenalCortex Medula

Glucocorticoid (cortisol), mineralocorticoid, androgen

Catecholamin : adrenalin. noradrenalin

Metabolic effect Immune system :-Immune activity-Cytokines-Inflammation

Stress

Hypothalamus

GHRH CRH Dopamin (PIH)

PRF TRH GnRH

Anterior Pituitary

GH ACTH Prolactin Prolactin Prolactin ProlactinLH , FSH

- Growth- Anabolisme Prolactin

Immune System- Regulation cytokine- IL10, IL12

Corpusluteum Reproductive Function

Stimulate LH progesterone

Inhibit 20α-HSD progesterone

S t r e s s

Desidua (Maternal)

• Prolaktin didalam Desidua :

1. Implantasi dan plasentasi

- Deferensiasi sel epitel

- Pertumbuhan trofoblast

- Angiogenesis

- Regulasi Immun

2. Gen yang berbahaya untuk kehamilan dilawan

(termasuk IL6 dan 20α-HSD)

• Prolaktin didalam Sirkulasi : Efek pada desidua ?

Pregnancy

Progesterone

PIBF Progesterone Receptor

Fetomaternal Interface

Th 1 Th 2 Dendritic Cells( IL2, 12, 18, IFNγ, TNF ) ( IL4, 5,6, 10, 13)

Stress

Note : Glucocorticoid ( cortisol ) & 11β-HSD Decidua Progesterone, Prolactin ??

Diagram manifestasi hormonal akibat stres maternal

Diagram gangguan keseimbangan hormonal maternal akibat stres

Managemen Stres pada Kehamilan

• Stres :

1. Berupa fisik, psikik, hormonal,

lingkungan

2. Bersifat berat/ringan, akut/kronis

• Penyakit (kelainan) mental :

akibat dari rangsangan stres yang cukup kuat dan lama.

Managemen Stres pada Kehamilan

• Terapi Stres :

1. Prinsip menghindari stres

2. Dukungan sosial

3. Konseling

4. Psikoterapi

5. Medikomentosa (untung rugi efek

samping)

Ringkasan

• Stres interaksi kompleks sistem neuro–endokrin-imun (HPA-HPG-Imun).

• Stres awal kehamilan : 1. Progesterone 2. PIBF 3. Prolactin 4. Th1 cytokines : Th2 cytokines 5. GC (Glucocorticoid / Cortisol) ?

• Berakibat : kegagalan pregnancy or fetal programming