Adolescence and Puberty MCB 135E Lecture 29

ADOLESCENCE: Period extending from onset of reproductive function to adulthood; characterized by maturation of all functions By adolescence, some functions are already established and continue to grow/develop until optimal function in adulthood The reproductive function is NOT developed by adolescence and develops during adolescence in males: persists throughout life in females:ceases at menopause

Why is reproductive function so late to mature? PUBERTY: Maturation of reproductive function is only one of many physiologic changes occurring at adolescence Why is reproductive function so late to mature? Immaturity is not at the level of the gonads or the anterior pituitary BUT at the level of the BRAIN (primarily limbic structures and hypothalamus)

Status of Gonadal Function in Children Testis and ovary are differentiated as are the secondary male and female organs Very low levels of sex hormones: testosterone (T) for males and estrogens (E) for females Very low levels of GnRH (in hypothalamus) and FSH/LH (in anterior pituitary) Therefore the negative feedback regulation does NOT seem to be operative at this age

Status of Gonadal Negative Feedback Regulation in Adults Levels of sex hormones inhibit GnRH release from hypothalamus Levels of GnRH reduce FSH/LH release from anterior pituitary Levels of FSH/LH cease to stimulate testis or ovary to secrete T and E Levels of sex hormones in blood stimulate GnRH release stimulating FSH/LH release Levels of FSH/LH stimulate T and E secretion. Thereby, normal sex hormone levels are established in blood and tissues.

FSH/LH (anterior pituitary) During Childhood Blood sex steroids FSH/LH (anterior pituitary) GnRH (hypothalamus) During Puberty Limbic system matures and, in preparation to maturation of sexual function, signals GnRH neurons to increase their responsiveness to changes in sex hormone levels.

CNS Status in Children At birth and in childhood, brain/head are proportionately more developed than other organs CNS matures progressively from birth to late childhood by: Dendritic branching & number of synapses: better communication Glial cell number: better metabolism, neurotransmission, myelination, faster and more efficient neuronal communication, specific stimulus: learning social interactions Threshold to stimuli is decreased, therefore neurons are responsive to lower intensity stimuli Of particular significance for the maturation of the reproductive function is the maturation of the limbic system

Limbic System: Major Functions Cognition Affect Conation (urge to take action) Feeding Behavior Sexual Behavior (urge to copulate, coordinate sequence of events in males and females that lead to pregnancy) Fear and Rage Motivation

Major Structures: Amygdala and Hippocampus, Septal nuclei Some Limbic-Hypothalamic Pathways: Stria Terminalis, Amygdala-hypothalamic fibers

Limbic System

Why is Reproductive Function so Late to Mature? Is the immaturity at the level of the hypothalamus? YES! Is it at the level of the anterior pituitary? No. Is it at the level of the gonads? Is it at the level of limbic-hypothalamic pathways? YES!

How do we know that the limbic-hypothalamic system is responsible for the immaturity of the reproductive system before puberty? 1. The immature gonads transplanted into an adult animal will mature immediately and demonstrate a normal reproductive function. 2. The pituitary, taken from a prepubertal animal and transplanted into an adult animal, will regulate a normal reproductive function. 3. Alterations/lesions/trauma of the hypothalamus and specific areas in the limbic system (amygdala, hippocampus) will prevent the prepubertal animal to develop a normal reproductive function

Hypothalamus as a “Gonadostat” With adolescence, the threshold to low sex hormone levels decreases thereby inducing stimulation of GnRH neurons & initiating the cascade of hypothalamo-pituitary-gonadal hormones and their feedback regulation

Changes in the “Gonadostat” & Onset of Reproductive Function Before puberty: secretion of GnRH and Gns is inhibited by the very low levels of gonadal steroids At puberty: decreased sensitivity to negative feedback of gonadal hormones on hypothalamic GnRH and pituitary FSH/LH synthesis & release establishes normal reproductive function

A. Maturational changes evoke potentials in the amygdala of the developing rats. A. Amygdala B. Hypothalamus B. Maturational changes evoke potentials in the hypothalamus of developing rats. Time Table Maturational Events 10 days: eye opening 21 days: weaning 39 days: maturation of reproductive function Adult

Maturational Changes in the Brain of the Rat (sagittal section) 10 Days: eyes opening 21 Days: Weaning 39 Days: Maturation of Reproductive Function