CICLO MENSTRUAL
•
Interação coordenada entre HHG (ovários) e trato genital
•
→ fenômeno ciclico e previsível denominado ciclo mesntrual
•
→ 2 fases: folicular ou proliferativa e luteal ou secretora
•
Limites do ciclo compreende o período entre o inicio do
sangramento menstrual episódico até o início do próximo
sangramento
•
Duração média: 25 a 30 dias
•
Fase luteal é bastante constante aproximadamente = 14 dias
Eixo hipotálamo-hipófise-ovário
GnHR (LHRH) – decapeptídeo
LH e FSH – glicoproteicos (α e β)
Estrógenos e progesterona (esteroides)
Padrões secretórios:
Infradiano – 30d
Circadiano - puberdade
Ultradiano – 1 pulso/h
Patterns of pulsatile LH secretion during the menstrual cycle. A. Representative examples during the follicular phase. Days are
calculated as from the LH surge. Note the high frequency of pulsatile LH release representative of a high GnRH pulse frequency in
this phase. EFP, early follicular phase; MFP, mid follicular phase; LFP, late follicular phase. B. Representative examples during the
luteal phase. Days are calculated as from the LH surge. Note the reduction in LH pulse frequency and a corresponding increase in
pulse amplitude, representative of the slowing down of the GnRH pulse generator in this phase. ELP, early luteal phase; MLP, mid
luteal phase; LLP, late luteal phase.
(Filicori
M, Santoro N, Merriam GR, Crowley WF: Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle. J Clin Endocrinol
Metab 62: 1136, 1986; used by permission of The Endocrine Society.)
Modulation of the FSH:LH ratio by changes in GnRH pulse frequency in a
monkey. Note the dramatic increase in the ratio with the decrease in GnRH
pulse frequency.
(Wildt L, Hausler A, Marshall G et al: Frequency and amplitude of gonadotropin-releasing hormone stimulation and gonadotropin
secretion in the rhesus monkey. Endocrinology 109: 376, 1981; used by permission of The Endocrine Society.)
FOLÍCULOS PRIMORDIAIS E FOLÍCULOS EM CRESCIMENTO
Follicle recruitment and selection. At the start of each menstrual cycle, an increase in FSH allows a
cohort of antral follicles (2–5 mm in diameter) to be recruited (cyclic recruitment) and escape
apoptotic demise. From this cohort, a leading (dominant) follicle emerges (selection), resulting in the
demise of the other follicles in the cohort. This dominant follicle undergoes final growth and
maturation, and ovulation.
(McGee EA, Hsueh AJ: Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21: 200, 2000; used by permission of The Endocrine Society.)
CORPO
LÚTEO
Células da
teca
luteinizadas
Células da
granulosa
luteinizadas
Mean plasma
concentrations of
inhibin A and inhibin B
(upper panel)
compared to estradiol
and progesterone
(center panel), and LH
and FSH (lower panel)
during the menstrual
cycle. Day 0 is the day
of the LH surge.
(Groome NP, Illingworth PJ, O’Brien M et
al: Measurement of dimeric inhibin B
throughout the human menstrual cycle. J
Clin Endocrinol Metab 81: 1401, 1996;
used by permission of The Endocrine
Society.)
DIMEROS
Classe
Atividade
Complexo
Subunidade 1
Subunidade 2
INIBINA
INIBE SECREÇÃO
FSH
INIBINA A
A (α)
βA
INIBINA B
A (α)
βB
ATIVINA A
βA
βA
ATIVINA AB
βA
βB
ATIVINA B
βB
βB
ATIVINA
ESTIMULA
SECREÇÃO FSH
Hillier, SG, Paracrine support of ovarian stimulation, 2009, Molecular Human Reproduction, vol 15, no 12: 843-850
LH
FSH
LHR
FSHR
Célula
Tecal
Célula
Granulosa
Teca Interna
Cam. Granulosa
Colesterol 
Estradiol 
Estrona 
Androstenediona 
Folículo Ovariano
L
LHR
Corpo Lúteo
LH
FSH
LHR
FSHR
Transporte esteróides sexuais:
%livre
Esteróide
Estradiol
Progesterona
Androstenediona
Testosterona
Cortisol
2
2
7
2
4
CBG
0
18
0
0
90
% ligada
SHBG
Albumina
38
60
0
80
8
85
65
33
0
6
CBG: globulina ligadora de corticosteróide
SHBG: globulina ligadora de esteróides sexuais (ou GBG)
Model for progesterone receptor (PR) genomic and non-genomic actions.
Progesterone diffuses across the cell membrane and binds to the PR in the cytoplasm of target cells, inducing:
conformational changes in the receptor,
dissociation of molecular chaperones (including heat shock proteins (HSP), p23 and immunophilins (I)),
dimerization and nuclear translocation.
In the classical mechanism of action, the PR dimer binds to specific DNA response elements situated in the regulatory regions of target genes
and recruits coactivators, such as p160s, histone acetyltransferases and the cyclin A/Cdk2 complex, and other components of the general
transcription machinery enabling RNA synthesis.
PRs also regulate transcriptional activity of other transcription factors (TFs) through:
protein–protein interactions and
coactivator recruitment rather than direct DNA binding.
Moreover, progestins activate kinase cascades such as Src and MAPK, which leads to phosphorylation of a variety of transcription factors.
-
DESENVOLVIMENTO DAS CARACTERÍSTICAS
SEXUAIS SECUNDÁRIAS – Alterações cíclicas
GLÂNDULAS MAMÁRIAS
E - crescimento ductal e tecido adiposo
P – crescimento dos lóbulos e alvéolos
ÚTERO e Trompas (miometrial)
E - ↑ proteínas contrateis, excitabilidade
P – antagoniza efeitos dos E
EPITÉLIO VAGINAL
E – cornificado
P – muco espesso, proliferação e infiltração de
leucócitos
GLÂNDULAS ENDOCERVICAIS (muco)
E – fino e alcalino
P – espesso, viscoso e celular
SNC
E- proliferação dendritos
P – eleva a temperatura corporal
OSSOS
E – ação positiva sobre os osteoblastos – estado
de mineralização adequado
TECIDO ADIPOSO
E -  deposição de gordura SC e mamas
METABOLISMO
E - ↑ viscosidade sanguínea, ↑ HDL, ↓ LDL, ↑
produção de células vermelhas
Estrógenos:
Mecanismos
de ação
Intracellular signaling pathways used to regulate the activity of estrogens, estrogen receptors, and selective estrogen receptor
modulators on articular tissues.
Pathway 1: canonical estrogen signaling pathway (estrogen response element (ERE)-dependent) - ligand-activated estrogen receptors (ERs)
bind specifically to EREs in the promoter of target genes.
Pathway 2: non-ERE estrogen signaling pathway - ligand-bound ERs interact with other transcription factors, such as activator protein (AP)-1,
NF-κB and Sp1, forming complexes that mediate the transcription of genes whose promoters do not harbor EREs. Co-regulator molecules
regulate the activity of the transcriptional complexes.
Pathway 3: non-genomic estrogen signaling pathways - ERs and GP30 localized at or near the cell membrane might elicit the rapid response
by activating the phosphatidylinositol-3/Akt (PI3K/Akt) and/or protein kinase C/mitogen activated protein kinase (PKC/MAPK) signal
transduction pathways.
Pathway 4: ligand-independent pathways - ERs can be stimulated by growth factors such as insulin-like growth factor (IGF)-1, transforming
growth factor-β/mothers against decapentaplegic (TGF-β/SMAD), epidermal growth factor (EGF) and the Wnt/β-catenin signaling pathway in
the absence of ligands, either by direct interaction or by MAP and PI3/Akt kinase-mediated phosphorylation. Since members of these
signaling pathways are transcription factors, some of them, such as SMADs 3/4, can elicit estrogen responses by interacting with ER in the
non-ERE-dependent genomic pathway. ERK, extracellular signal regulated kinase; GF, growth factor; GFR, growth factor receptor; MNAR,
Modulator of nongenomic action of estrogen receptors; TF, transcription factor.
Roman-Blas et al. Arthritis Research & Therapy 2009 11:241 doi:10.1186/ar2791
3-4 semanas de gestação:
células germinativas primordiais
no saco vitelínico
6ª semana: migração para crista
gonadal e continuam processo de
proliferação via mitoses
►ovogônias
10-12ª semana: início meiose
►ovócitos I
16ª semana: folículos primordiais
Maximo celulas
germinativas!