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ПОЛОВОЕ ДИФФЕРЕНЦИРОВАНИЕ [ sex differentiation ] (1802, лат.: differo - различаться).
Половое дифференцирование - это структурно-функциональная модификация частей живого организма в процессе их развития. Результатом полового дифференцирования является формирование пола особи.
Половое дифференцирование представляет собой последовательность процессов:
хромосомный пол −► гонадный пол −► фенотипический пол.
Несмотря на то, что в предопределении пола особи первостепенное значение имеет генетика, характер развития фенотипического пола определяет отношение интенсивностей синтеза половых гормонов: эстрогенов и андрогенов. Половые гормоны являются также средством регулирования процессами полового размножения (репродукции).
Средствами регулирования процессами развития и репродукции кроме половых гормонов являются гонадотропные гормоны гипофиза (лютеинизирующий гормон, фолликулстимулирующий гормон, пролактин), адренокортикотропный гормон коркового вещества надпочечников, хорионический гонадотропный гормон плаценты, простагландины различных органов.
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Схема. Дифференцирование.
Модификация: Underwood J.C.E. General and Systematic Pathology, 4th ed. Churchill Livingstone, 2004, 856 p., см.: Медицина: Литература. Иллюстрации.
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Примечание:
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Факторы, которые влияют на детерминирование, дифференцирование, регулирование и модулирование функций клеток во время эмбриогенеза: гормоны, паракринные факторы, факторы позиционирования, факторы роста, внешние факторы (витамины, канцерогены). |
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Схема. Дифференциально окрашенная (G-banded) X-хромосома = G-banded X chromosome.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Diagrammatic representation of G-banded X chromosome. Selected X-linked genes are shown (ATRX, б-thalassemia,
X-linked mental retardation; DAX1, DSS-AHC-critical region on the X chromosome gene 1; DIAPH2, human homolog of the Drosophila diaphanous
gene; DMD, duchenne muscular dystrophy; GK, glycerol kinase; GPD, glucose-6-phosphate dehydrogenase; MAMLD1, mastermind-like
domain-containing 1; MIC2, a cell surface antigen recognized by monoclonal antibody 12E7; PRKX, a member of the cAMP-dependent serinethreonine
protein kinase gene family [illegitimate X-Y interchange occurs most frequently between PRKX and PRKY]; RPS4X, ribosomal protein
S4; SHOX, short-stature homeobox gene; SOX3, SRY-like HMG box-3; USP9X, human x-linked homolog of the drosophila fat facets-related gene
[DFFRX]; XIC, X-inactivation center; XIST, Xi-specific transcripts). 2_164, p. 481 |
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Схема. Дифференциально окрашенная (G-banded) Y-хромосома = G-banded Y chromosome.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Diagrammatic representation of a G-banded Y chromosome (AZF, azoospermic factor; DAZ, deleted in azoospermia; MIC2,
gene for a cell surface antigen recognized by monoclonal antibody 12E7; PRKY, a member of the cAMP-dependent serine-threonine protein
kinase gene family; RPS4Y, ribosomal protein S4; SHOX, short stature homeobox gene; SRY, sex-determining region Y; TSPYA,B, members of the
testes-specific factor gene family; ZFY, zinc finger Y). 2_164, p. 482 |
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Схема. Главные гены, вовлечённые в половое дифференцирование от промежуточного мезодерма до бипотенциальных гонад.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Major genes involved in sex determination from the intermediate mesoderm to the bipotential gonad. (DMRT1, doublesex
and mab-3-related transcription factor 1; PGC, primordial germ cell [arise from an extragonadal site]; SF-1, steroidogenic factor 1; SOX9, SRY-like
HMG-box 9; WT1, Wilms tumor suppressor gene-1) The bipotential gonad contains the precursor cells which differentiate into the supporting
cells, steroid hormone-producing cells, and germ cells as shown. 2_164, p. 482 |
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Схема. Активация полового дифференцирования. Антагонистические управляющие сигналы генов.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Opposing gene signals (differential activation) determines fate of primordial gonad as a testis or ovary. RSPO1, respondin 1;
WNT4 , human homolog of Drosophila wingless gene; FOXL-2, forkhead box L2; в-catenin, key-regulated effector of the WNT-signaling pathway.
DAX-1 (DSS-AHC-critical region on the X chromosome gene 1) RSPO1 activates the WNT4/в-catenin canonical-signaling pathway which
inhibits SOX9 expression and promotes ovarian differentiation. SRY upregulates SOX9 by binding to testicular enhancing elements in the SOX9
gene (TESCO), and both SRY and SOX9 (in mice) inhibit the в-catenin canonical-signaling pathway and promote Sertoli cell and consequent
testicular development. A feed-forward loop involving SF-1 and FGF-9 has been demonstrated in mice which maintains SOX9 expression.
FOXL2 “knockout” in mice causes gonadal sex reversal, i.e., ovary to testes suggesting that FOXL2 inhibits SOX9 expression. No human
homozygous FOXL2 null mutations have been reported as yet. Duplication of DAX1 or WNT4 results in inhibition of testicular development
and atypical genitalia—dysgenetic 46,XY DSD. MAP3K4, mitogen-activated protein kinase 4; CBX2, chromobox homologue 2. It has been suggested
that CBX2 is upstream of SRY. More complete understanding of the exact function of MAP3K4 remains to be elucidated. 2_164, p. 483 |
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Схема. Половое дифференцирование плода человека.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Schematic sequence of sexual differentiation in the human fetus. Note that testicular differentiation precedes ovarian differentiation.
(Reproduced, with permission, from Grumbach MM, Hughes IA, Conte FA. Disorders of sex differentiation. In: Larsen PR, et al, eds.
Williams Textbook of Endocrinology . 10th ed. WB Saunders; 2003. Modified from Jost A. Hormone factors in sex differentiation of the mammalian
fetus. 2_164, p. 485 |
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Примечание:
Embryonic differentiation of male and female genital ducts from Wolffian and Mьllerian primordia.
A. Indifferent stage showing large mesonephric body.
B. Female
ducts. Remnants of the mesonephros and Wolffian ducts are now termed the epoophoron, paroophoron, and Gartner duct.
C. Male ducts before descent into the scrotum. The only
Mьllerian remnant is the testicular appendix. The prostatic utricle (vagina masculina) is derived from the urogenital sinus. 2_164, 487 |
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Примечание:
Embryonic differentiation of male and female genital ducts from Wolffian and Mьllerian primordia.
A. Indifferent stage showing large mesonephric body.
B. Female
ducts. Remnants of the mesonephros and Wolffian ducts are now termed the epoophoron, paroophoron, and Gartner duct.
C. Male ducts before descent into the scrotum. The only
Mьllerian remnant is the testicular appendix. The prostatic utricle (vagina masculina) is derived from the urogenital sinus. 2_164, 487 |
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Примечание:
Embryonic differentiation of male and female genital ducts from Wolffian and Mьllerian primordia.
A. Indifferent stage showing large mesonephric body.
B. Female
ducts. Remnants of the mesonephros and Wolffian ducts are now termed the epoophoron, paroophoron, and Gartner duct.
C. Male ducts before descent into the scrotum. The only
Mьllerian remnant is the testicular appendix. The prostatic utricle (vagina masculina) is derived from the urogenital sinus. 2_164, 487 |
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Схема. Каскад главных генов, определяющих дифференцирование мужского пола.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Hypothetical diagrammatic cascade of major genes involved in male sex differentiation (DAX1 , DSS-AHC-critical on the
X chromosome gene 1; GATA4, transcription factor; SF-1, steroidogenic factor 1; SOX9 , SRY homeobox gene 9 ; WT1 , Wilms tumor suppressor
gene). (Modified from Grumbach MM, Hughes IA, Conte FA. Disorders of sex differentiation. 2_164, p. 488 |
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Схема. Дифференцирование мужских наружных половых органов под влиянием дигидротестостерона.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Sex differentiation of the external genitalia of males is induced by dihydrotestosterone (DHT) which is synthesized in the
cells of the external genitalia from fetal testicular testosterone by the enzyme 5alpha-reductase-2. DHT may also be produced via the “back
door pathway”. Male differentiation of the external genitalia occurs from 8 to 12 weeks of gestation when aromatase activity of the liver and
placenta is relatively low. During this critical window of dimorphic sexual differentiation, the fetal adrenal transiently expresses 3в-HSD-2, resulting
in adrenal secretion of cortisol and a consequent downregulation of fetal ACTH and T precursor (DHEA-S) secretion from the fetal adrenal as
well as putative adrenal testosterone secretion. Thus, the female external genitalia are protected from T/DHT exposure and virilization during
this period when aromatase activity is low. After 12 weeks of gestation, 3в-HSD-2 activity in the adrenal is extinguished until 24 weeks of gestation
resulting in an increase in DHEA-S (T precursor) from the fetal adrenal. However, increased placental aromatase activity and a decrease in
androgen receptor activity in the labioscrotal folds of 46,XX females occurs so that excess T/DHT exposure after 12 weeks of gestation results
only in clitoromegaly.. 2_164, p. 489 |
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Схема. Синтез тестостерона в надпочечниках и в яичках.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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The enzymatic pathway of testosterone synthesis in the adrenal and testes is shown in blue on the left. A backdoor pathway first described by Wilson and Auchus from
studies in marsupials is shown on the right. This pathway utilizes 17-OH progesterone to synthesize dihydrotestosterone independent of testosterone synthesis. The backdoor pathway as
well as traditional testosterone synthesis by the fetal testis may be essential for normal male external genitalia differentiation. It has been suggested that virilization in 46,XX individuals
with CAH (such as 21-hydroxylase, 11-hydroxylase, P450 oxidoreductase, and possibly 3в-HSD-2 deficiency) who have elevated levels of 17-OH progesterone in utero may involve DHT synthesis
via the backdoor pathway. The fetal adrenal is relatively 3в-HSD-2 deficient from 12 to 24 weeks of gestation and DHEA-S is primarily secreted and converted in the liver to 16-OH
DHEAS. DHEA-S is converted by placental sulfatase to DHEA which then is metabolized to T and subsequently to estradiol by placental aromatase. Similarly, 16OH-DHEAS is aromatized to
estriol. Androstenedione can be directly converted to estrone by (3б-HSD-3 (AKRCs), 3-alpha-hydroxysteroid dehydrogenase-3; b5, cytochrome b5; 3в-HSD-1, 3-beta-hydroxysteroid dehydrogenase
type 1; 3в-HSD-2, 3-beta-hydroxysteroid dehydrogenase type 2; 17в-HSD-1, 17-beta hydroxysteroid dehydrogenase type 1; 17в-HSD-3, 17-beta-hydroxysteroid dehydrogenase
type 3; CY17, CYP21, 21 hydroxylase; CYP11B1, 11 hydroxylase;17hydroxylase; DHEA, dehydroepiandrosterone; P450scc, P450 side chain cleavage; POR, P450 oxidoreductase; StAR, steroidogenic
acute regulatory protein; Sulf2A1, sulfatase). 2_164, p. 489 |
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Схема. Механизм действия тестостерона на клетки-мишени.
Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
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Примечание:
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Diagrammatic representation of the mechanism of action of testosterone on target cells. Testosterone (T) circulates in
association with sex hormone–binding globulin (SHBG) but dissociates to enter the cells, where it is either 5б-reduced to dihydrotestosterone
(DHT) or aromatized to estradiol (E2). Dihydrotestosterone binds to the androgen receptor (AR) in the cytoplasm and activates it with the
release of heat shock proteins (HSP). The activated AR complex is then translocated to the nucleus, where it binds as a dimer to specific hormone
response elements of the DNA and, along with coactivators (eg, ARA), initiates transcription, leading to protein synthesis with consequent
androgenic effects. 2_164, p. 491 |
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СИСТЕМА РЕПРОДУКЦИИ: ОГЛАВЛЕНИЕ
СИСТЕМА РЕПРОДУКЦИИ: ТАБЛИЦЫ
СИСТЕМА РЕПРОДУКЦИИ: ИЛЛЮСТРАЦИИ
СИСТЕМА РЕПРОДУКЦИИ: ЛИТЕРАТУРА
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«Я У Ч Е Н Ы Й И Л И . . . Н Е Д О У Ч К А ?»
Т Е С Т В А Ш Е Г О И Н Т Е Л Л Е К Т А
Предпосылка:
Эффективность развития любой отрасли знаний определяется степенью соответствия методологии познания - познаваемой сущности.
Реальность:
Живые структуры от биохимического и субклеточного уровня, до целого организма являются вероятностными структурами. Функции вероятностных структур являются вероятностными функциями.
Необходимое условие:
Эффективное исследование вероятностных структур и функций должно основываться на вероятностной методологии (Трифонов Е.В., 1978,..., ..., 2015, …).
Критерий: Степень развития морфологии, физиологии, психологии человека и медицины, объём индивидуальных и социальных знаний в этих областях определяется степенью использования вероятностной методологии.
Актуальные знания: В соответствии с предпосылкой, реальностью, необходимым условием и критерием...
...
о ц е н и т е с а м о с т о я т е л ь н о:
— с т е п е н ь р а з в и т и я с о в р е м е н н о й н а у к и,
— о б ъ е м В а ш и х з н а н и й и
— В а ш и н т е л л е к т !
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