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Reproductive System

(Hormone Function)Physiology Department

Medical School, University of Sumatera Utara

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Endocrine Control: Three Levels of Integration

Hormones of the hypothalamic-anterior pituitary pathway

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Hypothalamus

Receives indirect sensory inputs from all sensory systemsSends neural outputs to various motor control nucleiSends neural outputs to sympathetic and parasympathetic nervous systemsSends both neural and hormonal outputs to pituitary

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Function of Hypothalamus

Integrates functions that maintain chemical and temperature homeostasis

Functions with the limbic system

Controls the release of hormones from the anterior and posterior pituitary

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Hypothalamus

Synthesizes releasing hormones in cell bodies of neurons

Hormones are transported down the axon and stored in the nerve endings

Hormones are released in pulses

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Hypothalamic Releasing Hormones

Seven releasing hormones are made in the hypothalamus

Thyrotropin-releasing hormone (TRH)

Corticotropin-releasing hormone (CRH)

Gonadotropin-releasing hormone (GnRH)

Growth hormone-releasing hormone (GHRH)

Growth hormone-release inhibiting hormone (GHIH)

Prolactin-releasing factor (PRF)

Prolactin-inhibiting hormone (PIH)

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Hypothalamus Releasing Hormones: Secretion

Is influenced by emotions

Can be influenced by the metabolic state of the individual

Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system

Delivered to the posterior pituitary via neural system

Usually initiates a three-hormone sequence

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Is also called the Adenohypophysis

Secretes tropic hormones in a pulsatile fashion

Synthesizes various hormones in various specific cell populations

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HYPOTHALAMIC HORMONE

EFFECTS ON THE ANTERIOR PITUITARY

Thyrotropin-releasing hormone (TRH)

Stimulates release of TSH (thyrotropin) and Prolactin

Corticotropin-releasing hormone (CRH)

Stimulates release of ACTH (corticotropin)

Gonadrotropin-releasing hormone (GnRH)

Stimulates release of FSH and LH (gonadotropins)

Growth hormone-releasing hormone (GHRH)

Stimulates release of growth hormone

Growth hormone-inhibiting hormone (GHIH)

Inhibits release of growth hormone

Prolactin-inhibiting hormone (PIH)

Stimulates release of prolactin

Prolactin-inhibiting hormone (PIH)

Inhibits release of prolactin

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Anterior Pituitary Hormones

Growth Hormone (GH, Somatotropin): primary hormone responsible for regulating body growth, and is important in metabolism

Thyroid-stimulating Hormone (TSH): stimulates secretion of thyroid hormone & growth of thyroid gland

Adrenocorticotropic Hormone (ACTH): stimulates cortisol secretion by the adrenal cortex & promotes growth of adrenal cortex

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Anterior Pituitary Hormones

Follicle-stimulating Hormone (FSH):

Females: stimulates growth & development of ovarian follicles, promotes secretion of estrogen by ovaries.

Males: required for sperm production

Luteinizing Hormone (LH):

Females: responsible for ovulation, formation of corpus luteum in the ovary, and regulation of ovarian secretion of female sex hormones.

Males: stimulates cell in the testes to secrete testosterone

Prolactin:

Females: stimulates breast development and milk production.

Males: involved in testicular function

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Neurohypophysis Hormones

Oxytoxin OT (pitocin)Stimulates smooth muscle contraction

Uterus & Mammary glands

RegulationActions

– Uterine stretching & Suckling

Works with estrogen

Inhibited by progesterone

Also made in uterine wall

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Oxytocin

releasepositive feedback

– uterine stimulation (stretch) and suckling stimulate the hypothalamus to release oxytocin from the posterior pituitary

– stimulates uterine contractions (labor) and milk letdown

– increases feedback for more oxytocin release

inhibited by lack of these stimuli

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Oxytocin

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Endocrine Regulation of Reproduction

Hypothalamus releases LHRH (GnRH) into hypothalamo-hypophyseal portal vessels.

Anterior pituitary secretes:LH (luteinizing hormone).

FSH (follicle-stimulating hormone).

Secreted in pulsatile fashion to prevent desensitization and down regulation of receptors.

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Endocrine Regulation

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Female Reproductive System

(Hormone Function)

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Pituitary-Ovarian Axis

Hormonal interactions between the anterior pituitary and the ovaries.

Anterior pituitary secretes FSH and LH.Controlled by GnRH.

FSH secretion is slightly greater than LH during early phase of menstrual cycle.LH secretion greatly exceeds FSH secretion just prior to ovulation.- feedback.

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Female Reproductive Cycle - Hormones

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Hormone Sources & Functions

Gonadotropin-releasing Hormone (GnRH) :

Source: Hypothalamus

Targets & Functions:Females & Males - Anterior Pituitary

– Stimulates the production of Follicle Stimulating Hormone (FSH) & Leutinizing Hormone (LH)

– Regulates the release of FSH & LH by the anterior pituitary gland

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Hormone Sources & Functions

Follicle Stimulating Hormone: Source: Anterior Pituitary

Targets & Functions:Females - Ovaries

– Stimulates follicle growth & maturation

– Stimulates estrogen production

Males - Seminiferous Tubules– Promotes sperm production

(Spermatogenesis) by establishing testosterone receptors on tubules

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Leutenizing Hormone:

Source: Anterior PituitaryTargets & Functions:

Females - Ovaries– Stimulates primary oocyte to complete

first meiotic division to become secondary oocyte

– Triggers ovulation of secondary oocyte– Transforms ruptured follicle into corpus

luteum

– Stimulates production of progesterone by corpus luteum

Males - Seminiferous Tubules– Stimulates sperm production

(Spermatogenesis) by causing interstitial cells in testes to secrete testosterone

Corpus luteum

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Estrogen:Sources: Maturing Follicles & Corpus Luteum

Targets & Functions:Body in general

– Stimulates the development of female secondary sexual characteristics

Breasts– Stimulates development of milk ducts

and sinuses (ampullae)

Uterus– Stimulates proliferative phase of

uterine cycle

Ovaries– Promotes oogenesis

Anterior Pituitary– Stimulates burst-like release of LH

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EstrogensEstrogens

• estradiol, estrone, estriol

• main site of production = ovaries but can also be produced in other tissues such as adipose

• bound to sex steroid binding globulin (SSBG)

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Steroid hormoneMainly oestradiolProliferation of endometriumThickening of vaginal epitheliumStimulate vaginal secretion (acid & very stringy – test for ovulation)Skeletal maintenanceEffects on brain and behaviour

ESTROGEN

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Reproductive Effects of EstrogensReproductive Effects of Estrogens

• growth/maturation of ovarian follicles

• increased motility of fallopian tubes

• endometrium growth

• thinning/alkalinization of cervical mucus

• stimulates uterine muscles

• increased uterine sensitivity to oxytocin

• breast development, fat deposition

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Progesterone:

Source:Corpus Luteum & PlacentaTargets & Functions:

Females - Uterus– Maintains thickened endometrium– Stimulates nutrient release– Quiets myometrium

Corpus luteumFemales - Breasts

– Stimulates development of alveoli for milk production

Females - Anterior Pituitary– Inhibits production & release of FSH &

LH

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Steroid hormoneIncreased appetiteDecreased uterine motility

Thickens cervical mucus

Progestational changes in the endometrium

Progesterone

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Oxytocin:

Sources: Manufactured by hypothalamus. Stored & released by Posterior Pituitary

Targets & Functions:Uterus

– Stimulates contraction of uterine myometrium causing lowering of fetus & labor

Breasts– Stimulates contraction of milk ducts

and sinuses, releasing milk

Positive Feedback Mechanisms:

1. Childbirth - Stretching of uterus and cervix

2. Suckling - Milk letdown reflex

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Prolactin:

Source: Anterior Pituitary

Targets & Functions:Breasts

– Stimulates alveoli of breasts to produce milk

Regulation

– Release of prolactin by anterior pituitary is regulated by hypothalamus production of Prolactin Releasing Hormone (PRH) & Prolactin Inhibiting Hormone (PIH)

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MENSTRUAL CYCLE

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Ovulation

One graafian follicle forms bulge on surface of ovary.

Extrudes secondary oocyte into the uterine tube.

LH causes the empty follicle to become corpus luteum which secretes:

Progesterone and estrogen.If not fertilized, becomes corpus albicans.

Insert fig. 20.33

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Siklus menstruasi

Dibagi atas 3 fase :

- Fase follikular (berlangsung 6 -13 hari)

- Fase ovulatory (hari ke 14)

- Fase luteal (berlangsung 14 hari)

Satu siklus rata-rata 28 hari

Awal siklus dihitung dari hari I haid

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Siklus Mentruasi

FSH mematangkan sel folikel

Pematangan sel folikel mensekresikan estrogen

Kadar estrogen memuncak sebelum hari ke 14→ feedback negatif ke hypothalamus

LH disekresikan

Folikel yang matang pecah →ovulasi Hari ke-14)

Bekas robekan →corpus luteum → progesteron >> dan setrogen <<

Kadar estrogen↑ dan progesteron ↑ → feedback negatif ke hypofise anterior

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Siklus Menstruasi

LH turun secara bermakna

Copus luteum degeneratif → corpus albicans

Progesteron turun kadarnya dalam darah

Menstruasi

Feedback positif

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Prolaktin

Peran: LAKTASI

Diatur oleh GnRH dan TRH

Dihambat oleh dopamin

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Proses Pengeluaran ASI

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Male Reproductive System

(Hormone Function)

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anterior pituitary drives changes during puberty

controlled by GnRH from hypothalamusbegins to secrete FSH, LH

LH – targets interstitial endocrinocytes

testosteronedihydrotestosterone (DHT)

FSH - Sustentacular cellsAndrogen-binding protein (ABP) concentrates androgens for spermatidsInhibin – negative feedback to the pituitary and hypothalamus

Hormones of brain-testicular axis

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Male Reproductive System

Testes:Seminiferous tubules:

Contain receptor proteins for FSH in Sertoli cells.FSH stimulates spermatogenesis to occur.

Leydig cells: LH stimulates secretion of testosterone.Contain receptor proteins for LH.

Insert fig. 20.12

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Control of LH and FSH Secretion

Negative feedback:Testosterone inhibits LH and GnRH production.

Maintain relatively constant secretion of LH and FSH.

– Declines gradually in men over 50 years of age.

– Testosterone converted to DHT, which inhibits LH.

Inhibin inhibits FSH secretion.

Aromatization reaction producing estradiol in the brain, is required for the negative feedback effects.

Insert fig. 20.13

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Onset of Puberty

FSH and LH secretion is high in newborn, but falls to low levels in few weeks.At puberty:

Brain maturation increases GnRH secretion.Decreased sensitivity of gonadotropin to negative feedback.

During late puberty, pulsatile secretion of LH and FSH increase during sleep.

Stimulate a rise in sex steroid secretion.

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Onset of Puberty (continued)

Stimulates rise in testosterone and estradiol-17.

Produce secondary sexual characteristics.

Age of onset related to the % of body fat and physical activity in the female

Leptin secretion from adipocytes may be required for puberty.

Insert fig. 20.10

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Testosterone:Sources: Interstitial Cells in Testes, adrenal korteks from androstenedione

Targets & Functions:Body in general

– Stimulates the development of male secondary sexual characteristics including:

» development of male genitalia» male skeleton and muscle development» male patterns for hair growth» increased RBC production & higher metabolic rate

Seminiferous tubules– Necessary for the completion of

spermatogenesis

Anterior Pituitary– Moderate inhibition of pituitary and hypothalamus

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Developmenttestosterone stimulates pattern development before birth (internal ducts)DHT external genitalsTestosterone converted to estrogens in brain brain development

Puberty – testosterone & DHT stimulate enlargement of male sex organs and secondary sexual characteristics

Hormones of brain-testicular axis

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Testosterone

At puberty testosterone prompts spermatogenesisCauses reproductive organs to grow & assume adult functionsAs adult normal levels of testosterone are required to maintain normal structure & function of reproductive organ

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Sertoli Cells

Form blood-testes barrier:Prevents autoimmune destruction of sperm.Produce FAS ligand which binds to the FAS receptor on surface to T lymphocytes, triggering apoptosis of T lymphocytes.

Prevents immune attack.

Secrete inhibin.Phagocytize residual bodies:

May transmit information molecules from germ cells to Sertoli cells.

Secrete androgen-binding protein (ABP):Binds to testosterone and concentrates testosterone in the tubules.

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Leydig CellsLeydig Cells

• produce/secrete testosterone

• located outside seminiferous tubules

• active in fetus till birth, puberty onward

• some testosterone converted to estradiol

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Estrogen Secretion

Sertoli and Leydig cells secrete small amounts of estradiol.

Receptors found in Sertoli and Leydig cells and accessory organs.

May be responsible for: Negative feedback in brain.Sealing of epiphyseal plates.Regulatory function in fertility.

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Leydig CellsLeydig Cells

• produce/secrete testosterone

• located outside seminiferous tubules

• active in fetus till birth, puberty onward

• some testosterone converted to estradiol

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Hormonal Control of Spermatogenesis

Formation of primary spermatocytes and entry into early prophase I, begin during embryonic development.

Spermatogenesis arrested until puberty.

Testosterone required for completion of meiosis and spermatid maturation.

Secrete paracrine regulators:IGF-1.

Inhibin.

Transforming growth factor.

FSH necessary in the later stages of spermatid maturation.

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