TEXTBOOK OF PEDIATRIC GYNECOLOGY - 2013

Chapter 4. EXAMINATION METHODS IN PEDIATRIC GYNECOLOGY

REGULATION OF REPRODUCTIVE FUNCTION IN GIRLS

The regulation of reproductive function in girls is carried out by a unified functional neuroendocrine system, which includes a central (integrating) component and peripheral (effector) Organs with a varying number of intermediate links.

Within the regulatory system of girls' reproductive function, individual links interact through direct and feedback mechanisms determined by The Nature of signals arriving from the periphery (Fig. 6).

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Fig. 6. Mechanisms of direct and feedback neurohumoral connections during the Menstrual cycle

The highest (first) level of Regulation of the girls' Reproductive System comprises structures that constitute the action result acceptor: The Nervous system, the amygdaloid complex, the hippocampus, and other hypothalamic structures. They influence the function of the Hypothalamus and Pituitary gland. This influence can be either stimulatory or inhibitory.

The Physiological effects of the highest regulatory level are mediated through neural and humoral pathways. A leading role in these interactions belongs to Brain Neurotransmitters (catecholamines, serotonin, acetylcholine, GABA, glutamic acid, enkephalins), which have been identified in extrapyramidal structures. Cerebral neurotransmitters regulate the hypothalamo-pituitary-ovarian levels of reproductive function. They determine circadian and ultradian rhythms, which are paramount to the functioning of the entire reproductive system.

Endogenous opioid Peptides (EOPs) are divided into three groups: enkephalins, endorphins, and dynorphins. They are found in various brain structures, the Autonomic nervous system, other Tissues and organs, as well as in the body's biological fluids (plasma, amniotic and follicular fluids, semen, etc.). They influence follicular maturation, the corpus luteum, ovulation, and the synthesis and release of Hormones by the hypothalamus and Pituitary Gland. This indicates their multifaceted impact on the regulation of the reproductive system and their involvement in The Development of its various pathological conditions. Using opioid receptor inhibitors such as naloxone and naltrexone, the inhibitory effects of EOPs on pituitary function, ovulation, and other generative processes are eliminated.

The Pineal Gland is a crucial neuroendocrine mediator in the regulation of the menstrual cycle. Methylindoles and peptides found in the pineal gland are divided into three groups according to their Biosynthesis site and physiological role: neurohypophyseal (Arginine-vasopressin, arginine-vasotocin, oxytocin, neurophysin), which receive information from the brain; adenohypophyseal (MSH, LH, FSH, GH, PRL), which transmit information regarding the regulatory capabilities of the Endocrine System; and the pineal gland's own hormone, melatonin, which inhibits LH and PRL levels. Melatonin is released rhythmically depending on the time of day (higher at night) and season (higher in winter). The pineal gland influences the regulation of Puberty, the functional state of the hypothalamus, pituitary gland, and Ovaries, Pregnancy, Lactation, and the development of A number of gynecological disorders.

The second level of regulation of reproductive function is the hypothalamus, specifically its hypophysiotropic area, which consists of Neurons of the ventromedial, dorsomedial, and arcuate nuclei. These structures exhibit neurosecretory activity involving liberins and statins. A special role in regulation belongs to luteoliberin, folliberin, and prolactostatin—the prolactin-inhibiting factor (PIF). PRL synthesis is stimulated by thyroliberin and, primarily, by dopaminergic structures. Dopamine inhibits prolactin release from pituitary lactotrophs, whereas its antagonists (methyldopa, reserpine, chlorpromazine) enhance its release (Fig. 7).

Fig. 7. Levels of regulation of the reproductive system

The ultradian neurosecretory function of the hypothalamus, modulated by impulses from extrahypothalamic structures and the Cerebral Cortex, is formed during puberty and indicates the maturity of hypothalamic neurosecretory structures. By regulating the hypothalamo-pituitary-ovarian system, it triggers generative function. The secretion of neurotransmitters and hormones by the hypothalamus is influenced by Blood estradiol levels.

The third level of regulation of reproductive function is the pituitary gland. It produces tropic hormones for peripheral Endocrine glands (FSH, LH, PRL, TSH, ACTH), among others. Gonadotropins interact with one another to influence ovarian function; FSH stimulates follicular growth and maturation, as well as estrogen secretion by follicles. The formation and activity of the corpus luteum are controlled by LH and PRL; the latter also controls mammary gland growth and lactation. Meanwhile, estrogens suppress the synthesis and release of FSH, and progesterone suppresses LH and PRL. Consequently, depending on the concentration and ratio of sex Steroid Hormones, The production of corresponding pituitary tropic hormones is either inhibited or activated.

Peripheral endocrine organs (ovaries, Thyroid Gland, Adrenal Glands) constitute the fourth level of regulation. The primary role belongs to the ovaries. Steroid biosynthesis and follicular development take place within the ovaries. Before menstruation, hormone levels in the follicular fluid rise sharply, particularly estradiol and FSH, resulting in an LH surge and ovulation—the rupture of the basement membrane of the dominant follicle and bleeding from the capillaries of the theca Cells. Ovulation occurs with the participation of Prostaglandins (F₂ and E₂), Proteolytic Enzymes, oxytocin, and relaxin. It is also influenced by external factors (Nutrition, stress, light and Temperature conditions), although Sex Hormones play the main role.

Luteoliberin levels rise, and against the Background of increased estradiol secretion and a subsequent LH peak—coupled with heightened pituitary sensitivity to luteoliberin—ovulation occurs. A decrease in PRL levels is recorded beforehand. This is followed by the next phase of the cycle: the luteal, or corpus luteum, phase. Progesterone levels rise, accompanied by the secretory transformation of the endometrium and other changes in various organs and body systems.

Follicular development with oocyte maturation, followed by the Development of the corpus luteum, proceeds simultaneously with the intensive biosynthesis of steroid sex hormones: estrogens, progesterone, and androgens. For the most part, androgens are synthesized in the adrenal cortex from dehydroepiandrosterone and dehydroepiandrosterone sulfate. Testosterone undergoes enzymatic aromatization into a more potent androgen, The amount of which in the female body reaches 50–75 µg per day. Androgens are synthesized in the theca cells, whereas estrogens are synthesized in the granulosa cells (Table 13).

Table 13. Concentration of steroid and Peptide Hormones in the blood of healthy girls during the maturation of the reproductive system from 1 to 17 years of age (V. F. Kokolina, 1997)

Inhibin, which inhibits pituitary FSH release, as well as locally active peptide substances such as oxytocin, relaxin, and prostaglandins, are also synthesized in the granulosa Cells of the follicles. Oxytocin exerts a luteolytic effect on the corpus luteum, whereas relaxin exerts a tocolytic effect on the myometrium.

Maximal hormonal activity across structures of all four levels is observed during the periovulatory period. In the event of peripheral hormone deficiency, pituitary cells become highly sensitive, responding to an equivalent concentration of releasing hormone with the release of a larger amount of gonadotropins. The functional state of all regulatory levels should be evaluated exclusively in close interrelation (Table 14).

Table 14. Normal urinary excretion rates of 17-ketosteroids and 17-oxogenic Steroids in girls (M. A. Zhukovsky et al., 1989)

The Influence of the adrenal glands on the regulation of reproductive function is mediated through the Hormones of the adrenal cortex and medulla. The adrenal cortex shares morphological similarities with the ovarian cortex, which accounts for the resemblance in the chemical Structure and biosynthetic cyclicity of their hormones. It is well established that various disruptions in corticosteroid Biosynthesis and METABOLISM lead to pathologies of ovarian hormonal function, causing a range of gynecological disorders; conversely, impairments in generative function lead to pathophysiological Changes in the adrenal cortex. A regulatory link between ovarian and adrenal Functions has also been established, involving the hypothalamus, pituitary gland, and neurotransmitter mechanisms.

The Role of The Thyroid Gland in regulating reproductive function is evident in both normal and pathological states, particularly during functional disorders such as hyper- and hypothyroidism. An excess of T₃ and T₄ leads to elevated LH levels, suppression of the ovulatory hormone surge, luteal phase defect, menstrual irregularities, and Infertility. A deficiency of THYROID HORMONES causes a decrease in FSH and LH synthesis, as well as suppression of ovarian function with subsequent manifestations of insufficiency.

Pathologies of the pituitary-thyroid system have a profound impact on the course of pregnancy and fetal development. While overt Clinical forms of thyroid disease cause various menstrual irregularities and infertility, subclinical forms are associated with pregnancy loss and other complications during gestation and fetal development.

The fifth level of the reproductive system comprises the FEMALE REPRODUCTIVE ORGANS and Mammary Glands, as well as the Skin, bones, and adipose tissue. Sex steroid hormones exert their effects on these structures, designating them as target organs. The cells of these tissues and organs possess sex Hormone Receptors, comprising cytoplasmic (Cytosol receptors) and nuclear receptors. Cytoplasmic receptors are strictly specific to estrogens, progesterone, and testosterone, whereas nuclear receptors can act as acceptors for aminopeptides, Insulin, and Glucagon. Glucocorticoids are considered functional antagonists to progesterone regarding receptor binding.

Sex hormone receptors have been identified in all structures of the reproductive system and in the Central Nervous System. The concentration of steroid receptors and their activity in reproductive organs, particularly in the endometrium, fluctuate in synchronization with the menstrual cycle, depending on circulating blood hormone levels. Receptors within the cells of the ovaries (for gonadotropins), the pituitary gland (for releasing hormones), and the hypothalamus (for neurotransmitters) are localized on The Cell membrane.

Hormone-receptor complexes interact with various structures of the target cell. Ultimate hormonal effects are manifested through metabolic pathways, driving numerous changes in the reproductive organs and all structures of the reproductive system that characterize the various stages of a woman's life under both physiological and pathological conditions.

The functioning of cellular receptor systems is genetically determined, which ultimately dictates the timing of puberty, the duration of a woman's life stages, and The activity of her reproductive system.