Repro Sys Puberty 2006, Concise

7/29/2019 Repro Sys Puberty 2006, Concise

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ENDOCRINOLOGY OF

THE REPRODUCTIVE SYSTEM,

PUBERTY AND MENOPAUSE

M. Djauhari Widjajakusumah


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The Hypothalamic-Pituitary Unit

GnRH Neurons in The Hypothalamus

Arcuate Nucleus

Important region for gonadotropin control in primate

The driver of the reproductive system

Generates and releases pulses of GnRH into the portal venous system

Median Eminence GnRH granules are transported by axonal flow to the median eminence

area; the most prominent projections are from arcuate neurons.

GnRH is released into capillaries Long Portal Veins pituitary stalk

adenohypophysis (anterior pituitary)

Direct brain - anterior pituitary vascular connection rapid transport ofundiluted minute amounts of GnRH


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The GnRH Pulse Generator

Arcuate nucleus

The foremost ventral portion of the medial basal hypothalamus

The most essential neural center controlling gonadotropin secretion

Lessions of the arcuate nucleus abolished basal release of LHand FSH

Increase in arcuate nucleus electrical activity precedes

LH discharge

Subject to modifying influences from extra- and intra-hypothalamic loci

Griffin, J.E., Ojeda, S.R.: Textbook of Endocrine Physiology 3 rd ed 1996.


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The GnRH Pulse

GnRH is released in pulsating fashion, concomitantly stimulates LH and FSH

secretion

Synchronized pulse of GnRH release and pulse of LH release:

Intermittent (fluctuated) LH release, ultradian (less than 1 day) rhythm

Oscillate with a period of about 1 hr; 2 hrly between peaks

Synchronized pulse of GnRH release and pulse of FSH release:

Lower amplitude of FSH pulse than that of LH:

smaller amounts of FSH released in response to GnRH pulse

longer FSH half-life individual pulses masking effects on the

subsequent ones

estradiol suppress FSH release at the pituitary level more evident inthe early follicular phase, postmenopausal period, ovariectomized

individuals (low estradiol conditions)


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Gonadotropin-Releasing System

Adenohypophysis gonadotroph cells

Cells secrete only LH, or only FSH, or both

Pulsatile secretion of gonadotropins

Particularly LH

Episodes 70-100 mnts

Interpulse intervals 1 hr (circhoral rhythm)

Less frequent during the luteal phase (progesterone effect?)

Sleep-related rhythm (diurnal rhythm)

increased LH release during sleep

fundamental feature at the onset of puberty A function of hypothalamic LHRH

Griffin, J.E., Ojeda, S.R.: Textbook of Endocrine Physiology 3 rd ed 1996.


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ADOLESCENCE AND PUBERTY

Adolescence

The period of growth and maturation of the reproductive system

that culminates at puberty

The final maturation of of the reproductive system activated bypituitary gonadotropins

Secretory and morphological activities of the gonads reach the

adult stage, and the menarche occurs


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Adolescence and Puberty

Puberty

Refers to the process of physical changes by which a child's bodybecomes an adult body capable of reproduction

The period when the endocrine and gametogenic functions of the gonadshave first developed to the point where reproduction is possible

Thelarche: development of breasts

Pubarche: development of axillary and pubic hair

Menarche: the first menstrual period Generally anovulatory Regular ovulation about a year later


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Control of The Onset of Puberty

The precise mechanism is still not well understood

Requires interactions between the brain, the pituitary gland, and thegonads and their target organs

Childrens gonads can be stimulated by gonadotropins

Childrens pituitary contain gonadotropins, but are not secreted

Childrens hypothalami contain GnRH

During the period from birth to puberty, a still unknown neural

mechanism is preventing the normal pulsatile release of GnRH


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CONTROL OF THE ONSET OF PUBERTY

THE NEURAL INPUT

The neuroendocrine GnRH system is fully mature at birth adultlevel of gonadotropin secretion

Pulsatile GnRH activity declines in late infancy until the prepubertal/adolescence phase (hypothalamic quiescence)

The initial step that leads to puberty is an restored increase in thepulsatile release of GnRH gonadotropins release puberty

Proper release of GnRH may require synchronous activity ofspecific neuronal system


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CONTROL OF THE ONSET OF PUBERTY

THE METABOLIC INPUT

Good nutrition advances the onset of puberty, starvation delays it

Link between nutrition and the activity of GnRH pulse generator

The hypothesis: a threshold of body weight (percent of body fat) is

critical for allowing initiation of the maturity process Probably metabolic cues are relayed to the brain and provide

signals that activate the GnRH pulse generator


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Reinitiation of Pulsatile Gonadotropin Secretion in Pubertal Children

The first sign of the initiation of sexual maturation

Low gonadotropin secretion during day-time, increased during thenight

In the later stages of puberty

Nocturnal increase of gonadotropin levels replaced gradually by

episodic increase around the clock The possible relation between melatonin and the onset of puberty

Melatonin is argued to inhibit the onset of puberty in humans; its

effects vary markedly from species to species (inhibition

facilitation)


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Puberty as a hormonal process

1. The brain's hypothalamus begins to release pulses of GnRH. Truepuberty is often termed "central puberty" because it begins as aprocess of the central nervous system

2. Cells in the anterior pituitary respond by secreting LH and FSH into thecirculation

3. The ovaries or testes respond to the rising amounts of LH and FSH bygrowing and beginning to produce estradiol and testosteron

4. Rising levels of estradiol and testosterone produce the body changesof female and male puberty


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PRECOCIOUS PUBERTY

Pubertal changes before the age of 8 years Isosexual precocious puberty: sexual development is consistent

with genetic sex

Heterosexual precocious puberty: sexual development is

inconsistent with genetic sex ( virilism)

True precocious puberty

Pseudoprecocious puberty


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PRECOCIOUS PUBERTY

TRUE PRECOCIOUS PUBERTY

The gonads are the source of the sex hormones

Premature activation of the hypothalamic-pituitary unit

Secondary sex characteristics with gametogenesis

PSEUDOPRECOCIOUS PUBERTY

Primary ovarian / testes (gonadal) abnormality independent of pituitary

stimulation

Leydig cell tumors of testis

Granulosa cell tumors of ovary

Adrenal (extragonadal) Androgen-secreting tumors (in males)

Estrogen-secreting tumors (in females)


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DELAYED PUBERTY

Lack of physical manifestation of puberty beyond the norm of pubertalage (17 in females, 20 in males)

Organic causes

CNS disorders: delay in activation of the hypothalamic pulse

generator

Gonadotropin deficiency

Gonadal failure (dysgenesis)

Environmental factors

Nutrtion

Weight Stress

Exercise


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Thank you

Repro Sys Puberty 2006, Concise

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