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Sistema endócrino

e exercício físico

Daniel Gonçalves
danielmgon@fade.up.pt
Efetores Suporte Reguladores

• Generalidades
• Estrutura e função do sistema endócrino
• Respostas endócrinas agudas ao exercício físico
• Adaptações do sistema endócrino ao exercício físico
Principais processos regulados pelo sistema endócrino

• Crescimento e desenvolvimento
• Reprodução
• Metabolismo celular e balanço energétio
• Balanço eletrolítico, H2O, nutrientes no sangue
• Sistema cardiovascular
• Defesa imunitária

Comunicação com órgão alvo através de mensageiros químicos

Sistema endócrino Sistema nervoso


Classificação das hormonas

Derivados de aminoácidos
• Restantes glândulas

Esteroides
• Gonadas
• Supra-renal (córtex)

Classificação das hormonas: implicações para transporte

Hormonas hidrossolúveis

Hormonas lipossolúveis
Interação das hormonas com o tecido-alvo
Especificidade

Localização dos receptores e mecanismo de acção das hormonas

(Resposta lenta)

(Resposta rápida)
Fatores que influenciam a magnitude do efeito no tecido-alvo

Concentração da hormona no plasma


• Taxa de secreção (estímulos inibitórios vs. excitatórios)
• Taxa de metabolização e/ou excreção
• Quantidade de proteínas transportadores (ex: hormonas esteroides
e T4)
• Volume plasmático

Receptores
• Presença vs. ausência num determinado tecido-> especificidade da
resposta
• Quantidade, na superfície celular
• Mais vs. menos
• Up vs down-regulation
• Complementaridade ligando-receptor
• Competição por afinidade
• Agonistas vs. antagonistas

Outros principios gerais da resposta hormonal

• A mesma hormona pode


exercer múltiplos efeitos
no mesmo orgão-alvo

• A mesma hormona pode


atuar em vários orgãos- cortisol
alvo
Mecanismo de regulação da secreção hormonal

Mecanismos de regulação da secreção hormonal


Orgão endócrinos

Clássicos Não-clássicos

Coração
• BNP
• ANP

Rim
• EPO
• Renina
• 1,25-di-hidroxi-vitamina D

Trato GI
• Incretinas
• Grelina

T. Adiposo
• Leptina
• Adiponectina

M. Esquelético
• IL-6
• Irisina

HIPOTÁLAMO E HIPÓFISE

• Hipotálamo e a hipófise são os principais locais de


interação do sistema nervoso com o sistema
endócrino

• Hipotálamo regula a atividade secretora da Hipófise

• Atividade secretora do hipotálamo regulada por


hormonas, informação sensorial e emoções
HIPOTÁLAMO E HIPÓFISE
Estrutura e funcionamento da neuro-hipófise ou hipófise posterior

Hormonas secretadas pela neurohipófise


• ADH (vasopressina)-> túbulos renais
• Oxitocina -> glândula mamária e miométrio

HIPOTÁLAMO E HIPÓFISE
Estrutura e funcionamento da adeno-hipófise ou hipófise anterior

Hormonas hipotalámicas
• CRH (+)
• TRH (+)
• GnRH (+)
• GHRH (+)/Somatostatina (-)
• Dopamina (-) /PRH (+)

Hormonas adeno-hipofisárias
• ACTH -> glândula adrenal
• TSH -> tiroide
• LH/FSH -> gónadas
• GH -> fígado, TA e m. esquelético
• Prolactina -> glândula mamária
ROLE OF THE ENDOCRINE SYSTEM IN EXERCISE

1. Hormonal Regulation of Metabolism • Insulin/Gucagon


• Mobilize fuel for the production of ATP energy needed to • GH
support muscle contraction • T3/T4
• Maintain blood glucose levels (because neural tissue can • Cortisol
use only glucose to produce energy) • Epinephrine and Norepinephrine

2. Hormonal Regulation of Cardiovascular Function • Epinephrine and Norepinephrine


• Enhance cardiac function • Aldosterone
• Distribute blood to active tissues • ADH
• Maintain blood pressure by stabilizing fluid and electrolyte
balance • Testosterone
• Estrogens/Progesterone
3. Hormonal Involvement in Muscle, Bone, and Adipose Tissue • Androgens
• Hormones involved in the structure and function of • Calcitonin
muscle, bone, and adipose cells are beyond the • Parathyroid hormone (PTH)
immediate goals of supporting acute exercise, but they • Leptin
may be importante during recovery and thus generally • Adiponectin
facilitate training adaptations • Growth hormone
• Insulin-like growth factors (IGF)

Hormonal Responses to Exercise


Insulin and Glucagon
Produzida e secretada pelo pâncreas endócrino
• Células β (60 a 70 %) -> Insulina, pro-insulina, péptido C e amilina
• Células α (20 a 25%) -> Glicagina

Função:
Insulina (preservar/acumular reservas)
• Fígado:
- ↓ Glicogenólise
- ↓ Gliconeogénese
- ↑ síntese de glicogénio
• Tecido adiposo:
- ↑ Captação de glicose
- ↓lipólise
• Músculo:
- ↑ GLUT4 > transporte de glicose
- ↑ síntese de glicogénio (reservas)
- ↑ glicólise e oxidação da glicose
- ↑ síntese proteica
- ↓ catabolismo proteico

Glicagina (mobilizar reservas)


• Fígado:
- ↑ glicogenólise
- ↑ gliconeogénese
• Tecido adiposo:
- ↑ lipólise
- ↓ captação de glicose
• Músculo:
- ↓ captação de glicose

Regulação:
• Humoral: glicemia, aminoácidos
• Hormonal: glicagina/insulina, somatostatina (-), incretinas (+)
• Neural: SNS (-) e SNP (+)
Hormonal Responses to Exercise
Insulin and Glucagon

Effect of duration Effect of intensity


(moderate-heavy submax intensity)

Papel no exercício físico:

• ↑ mobilizar reservas
• ↓ captação de glicose
(manutenção da glicemia)

Hormonal Responses to Exercise


Insulin and Glucagon

But if plasma glucose levels are relatively constant during exercise, what is modifying the secretion
of glucagon and insulin?
When the plasma glucose concentration is relatively
constant*, the sympathetic nervous system can modify the
secretion of insulin and glucagon.

*It must be mentioned that if there were a sudden change in the plasma glucose
concentration during exercise, these hormones would respond to that change
Hormonal Responses to Exercise
Insulin and Glucagon

Glucose is taken up 7 to 20 times faster during exercise than at rest—even with the decrease in plasma insulin

...how is this possible?

Rate of blood glucose oxidation


±1 g/min in heavy or prolonged
• ↑ Blood flow to exercising
(>3hours) moderate exercise muscle
- Receives more insulin and
glucose per unit of time

• ↑ GLU-4 recruitment by
insulin-independent
mechanisms

Nat Rev Endocrinol. 2017 Mar;13(3):133-148

Hormonal Responses to Exercise


Growth Hormone: aerobic exercise
Produção e secreção: adenohipófise

Função:
- Tecido adiposo (↓adiposidade)
• ↓ Captação de glicose
• ↑ Lipólise
- Músculo (↑massa magra)
• ↑ captação de A.A.
• ↑ Síntese proteica
• ↓ Captação de glicose
- Fígado
• ↑ Gliconeogénese
• ↑ IGF-1
- Crescimento (principalmente via IGF-1)
• Longitudinal
• Celular (nº e tamanho células)

Regulação:
- Hormonal: GHRH (+), Somatostatina (-), feedback negativo pela
GH e IGF-1
- Humoral: hipoglicemia (+)
- Neural: Stress (ex: exercício físico) (+)
Hormonal Responses to Exercise
Growth Hormone: aerobic exercise

Exercise is the most potent stimuli for GH secretion


GH increases during exercise GH increases following exercise

70% of VO2 peak


Hormonal Responses to Exercise
Growth Hormone: resistance exercise
1 3x 8 exercícios 2 3x 8 exercícios 3 3x 8 exercícios
1 5x 8 exercícios 2 5x 8 exercícios 3 5x 8 exercícios
5RM 10RM 5RM 10RM 5RM 5RM
3 min repouso 3 min repouso 1 min repouso 1 min repouso 1 min repouso 3 min repouso

High total work and short rest periods

Hormonal Responses to Exercise


Growth Hormone: role with exercise

• Preserve plasma glucose


- Direct but slow-acting effect on
carbs and fat metabolism
- To provide adequate fuel for
postexercise restorative
processes rather than the
conventional anabolic role that
is most typically associated with
postexercise increases in GH.
Growth hormone
and
performance?

Growth hormone and performance?

GH vs. Placebo
Growth hormone and performance?

Endocrine Reviews, 2019

Growth hormone and performance?

GH + Exercise in healthy adults

• GH promotes an increase in lean body mass, but this


is due more to an increase in water retention than
an increase in cell mass.

• GH + resistance training vs resistance training:


minimal gains in lean body mass, muscle mass, and
strength in normal, healthy men

• Adverse events (dose dependent): suppression of


the GH/IGF axis, water retention and edema, joint
and muscle aches, and an increased risk of injection-
related diseases

Ann Intern Med. 2007;146:104-115.


Ann Intern Med. 2008;148:747-758
Growth hormone and performance?

GH in older adults

• Improves body composition (increase in lean mass


and decrease in fat mass
• No change in strength
• Increased rates of adverse events

Ann Intern Med. 2007 Jan 16;146(2):104-15.

• Future studies:
- GH + testosterone (at lower doses)
- Combination with exercise

Hormonal Responses to Exercise


Adrenal hormones

Aldosterone

Cortisol

Dehidroepiandrosterona
(DHEA)
Hormonal Responses to Exercise
Cortisol

Produzida e secretada pelo córtex adrenal


• Zona fasciculata

Função:
Metabolismo
• ↑ Glicemia
• ↑ Captação de glicose
• ↑ Catabolismo
• ↑ Lipólise
• ↑ Gliconeogénese

Resposta ao stress
• Vasoconstrição permissiva via A/NA

Imuno-supressão
• Anti-inflamatório
• Inibe a produção de anticorpos

Regulação:
- Neural: stress, ritmo circadiano
- Hormonal: CRH (hipotálamo), ACTH (hipófise), cortisol (feedback
negativo)

Hormonal Responses to Exercise


Cortisol

Effect of duration Effect of intensity


• In short-duration and/or low- to moderate- (moderate-heavy submax intensity)
intensity activity
- Decrease (clearance exceeds secretion)

• Anaerobic exercise causes greater increases in


cortisol than aerobic exercise

• Dynamic resistance exercise causes large


increases both during and after high-intensity
sessions, probably because of its large
anaerobic component

• Cortisol levels in the blood remain elevated up


Secreção
to several hours after exercise
Metabolização
Excreção
Hormonal Responses to Exercise
Cortisol

• In short-duration and/or low- to moderate-intensity activity


- Decrease (clearance exceeds secretion)

• Anaerobic exercise causes greater increases in cortisol than aerobic


exercise

• Dynamic resistance exercise causes large increases both during and


after high-intensity sessions, probably because of its large anaerobic
component

• Cortisol levels in the blood remain elevated up to several hours after


exercise

• Role with exercise:


- Maintenance of plasma glucose
> Direct effect -> gene expression (slow-acting hormone)
> Permissive effect on substrate mobilization by allowing other
fast-acting hormones (Glucagon and Epinephrine) to deal with
FFA and glucose mobilization

Hormonal Responses to Exercise


Epinephrine and Norepinephrine (Catecholamines)

Produzida e secretada pela medula adrenal


• 80% adrenalina
• 20% noradrenalina

Função:
80%
20%

Regulação:
- Neural: stress (+)
- Humoral: hipoglicemia (+)
Hormonal Responses to Exercise
Epinephrine and Norepinephrine (Catecholamines)

Epinephrine Norepinephrine

• Catecholamine response to static exercise is larger than during


• Sources of catecholamines during exercise dynamic resistance exercise of equal heart rate or oxygen
- adrenal medulla (E and NE; slower) consumption
- SNS (NE; faster)
• Catecholamine levels depend on exercise duration (C, D) and • Catecholamine levels depend:
intensity (E, F) a) force of muscle contraction
• Catecholamine levels are intensity-dependent b) amount of muscle stimulated
c) amount of rest between reps

Hormonal Responses to Exercise


Epinephrine and Norepinephrine (Catecholamines)

Role of catecholamines in substrate mobilization


Hormonal Responses to Exercise
Thyroid

T3 e T4

Produzida e secretada pela tiroide

Função:
- Todos as células
• ↑ Metabolismo e produção de calor
• Crescimento e desenvolvimento (SNC)
- Vasos sanguíneos
• ↑ recetores beta-adrenérgicos

Regulação:
- Hormonal: TRH (hipotálamo), TSH (adenohipófise) e feedback
negativo (T3 e T4)
- Neural: hipotermia, stress

Hormonal Responses to Exercise


Thyroid

T3 and T4:
• increase with Aerobic Ex
• no change with Resistance Ex

↑ Uptake of T3 and T4 by tissues at


a faster rate
↓ circulating levels of T3 and T4
↑ TSH -> ↑ secretion of T3 and T4

• ROLE:
- maintenance of plasma glucose
-> Facilitate the work of other hormones
Increasing nº receptors and/or affinity
ex: without T3, epinephrine has little effect on the mobilization of FFA from adipose
tissue
ROLE OF THE ENDOCRINE SYSTEM IN EXERCISE
1. Hormonal Regulation of Metabolism • Insulin/Gucagon
• Mobilize fuel for the production of ATP energy needed to • GH
support muscle contraction • T3/T4
• Maintain blood glucose levels (because neural tissue can • Cortisol
use only glucose to produce energy) • Epinephrine and Norepinephrine

2. Hormonal Regulation of Cardiovascular Function • Epinephrine and Norepinephrine


• Enhance cardiac function • Aldosterone
• Distribute blood to active tissues • ADH
• Maintain blood pressure by stabilizing fluid and electrolyte
balance • Testosterone
• Estrogens/Progesterone
3. Hormonal Involvement in Muscle, Bone, and Adipose Tissue • Androgens
• Hormones involved in the structure and function of • Calcitonin
muscle, bone, and adipose cells are beyond the • Parathyroid hormone (PTH)
immediate goals of supporting acute exercise, but they • Leptin
may be importante during recovery and thus generally • Adiponectin
facilitate training adaptations • Growth hormone
• Insulin-like growth factors (IGF)

Hormonal Responses to Exercise


Epinephrine and Norepinephrine (Catecholamines)

Role of catecholamines in the Regulation of Cardiovascular Function


Hormonal Responses to Exercise

Plasma volume may decrease by


15% in just the first minutes of
exercise

↓ Blood volume
↑ Osmolarity

Hormonal Responses to Exercise


ADH/Vasopressin

Produzida no hipotálamo e secretada pela neurohipófise


Alvo: rins e arteríolas
Função:
- Prevenir excreção de água
- Vasoconstrição
Regulação:
- Humoral: ↑Osmolaridade
- Neural: ↓ Pressão arterial
- Neural: ↓ Volume circulante efetivo
Hormonal Responses to Exercise
ADH/Vasopressin

Role of ADH in the Regulation of Cardiovascular Function

Hormonal Responses to Exercise


Aldosterone

Produzida e secretada pelo córtex adrenal


• Zona glomerolosa

Função:
Controlo do volume circulante e pressão arterial
• ↑ Absorção de Na+
• ↑ Absorção de H2O
• ↑ Excreção de K+

Regulação:
• Hormonal: Angiotensina II, CRH (hipotálamo), ACTH (hipófise)
• Humoral: [K+] sangue
Hormonal Responses to Exercise
Aldosterone

Role of Aldosterone in the Regulation of Cardiovascular Function

ROLE OF THE ENDOCRINE SYSTEM IN EXERCISE


1. Hormonal Regulation of Metabolism • Insulin/Gucagon
• Mobilize fuel for the production of ATP energy needed to • GH
support muscle contraction • T3/T4
• Maintain blood glucose levels (because neural tissue can • Cortisol
use only glucose to produce energy) • Epinephrine and Norepinephrine

2. Hormonal Regulation of Cardiovascular Function • Epinephrine and Norepinephrine


• Enhance cardiac function • Aldosterone
• Distribute blood to active tissues • ADH
• Maintain blood pressure by stabilizing fluid and electrolyte
balance • Testosterone
• Estrogens/Progesterone
3. Hormonal Involvement in Muscle, Bone, and Adipose Tissue • Androgens
• Hormones involved in the structure and function of • Calcitonin
muscle, bone, and adipose cells are beyond the • Parathyroid hormone (PTH)
immediate goals of supporting acute exercise, but they • Leptin
may be importante during recovery and thus generally • Adiponectin
facilitate training adaptations • Growth hormone
• Insulin-like growth factors (IGF)
Hormonal Responses to Exercise
Testosterone
Produzida e secretada pelos testículos
• Céulas de Leydig

Função:
• Crescimento e maturação do sistema reprodutor
• Caracteres sexuais secundários masculinos
• Espermatogénese
• Distribuição do tecido adiposo
• Crescimento e força muscular
• Crescimento e densidade óssea

Regulação:
• Hormonal: GnRH (hipotálamo), FSH e LH (hipófise),
Testosterona e inibina (feedback negativo)

Hormonal Responses to Exercise


Testosterone

10-40% increase Source?


• different types of exercise (e.g., endurance vs. resistance); • Secretion (inconsistently reported) ?
• training intensity and/or duration of resting periods; • ↓ Plasma volume ?
• study populations (e.g., young vs. elderly; lean vs. obese; sedentary vs. athletes); • ↓ Metabolization and excretion ?
• the time point when serum testosterone was measured (e.g., during or • Peripheral conversion from adrenal
immediately after vs. several minutes or hours after the exercise). androgens?
Hormonal Responses to Exercise
Testosterone

Use of androgens in healthy adults

• Among elite athletes, the most commonly


detected drugs are testosterone, stanozolol,
and nandrolone.

• Androgen use causes, in a concentration-


dependent manner, increases in lean body
mass, muscle mass, and strength in men;

• When androgens and resistance training are


combined, greater gains are realized than with
either intervention alone;

Journal of Athletic Training 47: 567–588, 2012.


Drug and Alcohol Dependence 130: 208–214, 2013.
Sports Medicine 42: 119–134, 2012.

Hormonal Responses to Exercise


Testosterone

Use of androgens in healthy adults

• Adverse effects
• Men: suppression of the hypothalamic–
pituitary–gonadal axis, mood and
behavior disorders, increased risk of
cardiovascular disease, liver dysfunction
(with oral androgens), insulin resistance,
glucose intolerance, acne, and
gynecomastia (breast development),
cognitive deficits (in long-term anabolic
steroid user)

• Women: are similar to that of men, but


in addition, the androgens may have
virilizing effects, such as enlargement of
the clitoris, deepening of the voice,
hirsutism, and change in body build.
These changes may not be reversible
when androgen use is stopped.

Journal of Athletic Training 47: 567–588, 2012.


Drug and Alcohol Dependence 130: 208–214, 2013.
Sports Medicine 42: 119–134, 2012.
Hormonal Responses to Exercise
Produzida e secretada pelos ovários
• Progesterona
• Estrogénios
• Estradiol
• Estrona
• Estriol

Função:
Estrogénios
• Crescimento e maturação do sistema reprodutor feminino
• Caracteres sexuais secundários femininos
• Estimula desenvolvimento folicular
• Estimula ciclo uterino (fase proliferativa)
• Deposição de gordura
• Regeneração muscular
• Crescimento e densidade óssea
• Cardioprotetor
• Neuroprotetor
Progesterona
• Desenvolvimento das mamas
• Manutenção do endométrio (fase secretora)

Regulação:
• Hormonal: GnRH (hipotálamo), FSH e LH (hipófise), Estrogénio e inibina
(feedback negativo)

Hormonal Responses to Exercise

No change in LH and FSH…so…. Source


of P and E?
• ↔Secretion (LH/FSH)
• ↓ Plasma volume
• ↓ Metabolization and excretion
• Androgen conversion?

Acute exercise and menstrual cycle phase


• Anaerobic performance is not affected by menstrual cycle phase
• Impact of menstrual cycle phase in endurance performance is mixed
• The effect of menstrual cycle phase on metabolism is not clear
• Agreement that menstrual cycle phase DOES NOT impact VO2max, lactate, plasma volume HR or ventilation
response to exercise
• Risk of ACL injury is greater in the late follicular phase (10-14 days) -> increased knee laxity

Chronic (heavy) exercise and menstrual cycle


• Highest prevalence of menstrual disorders (up to 40% ) occurs among endurance or aesthetic sports athletes • Primary amenorrhea is characterized as a lack of menarche by age 15
years
(particullarly among those with lower BMI and lower percent body fat, higher training volumes, younger age)
• Oligomenorrhea is defined as menstrual cycles that are greater than
• Osteoporosis is common in athletes with secondary amenorrhea
35 days apart.
• Caused by low energy availability due to failure to maintain adequate nutrition and caloric intake or decreased • Secondary amenorrhea is characterized as an absence in menstruation
caloric intake for more than three cycles or six months in females who have had
regular menses.
Hormonal Responses to Exercise
Produzida e secretada pelo córtex adrenal Androgens
• Zona reticular
• Dehidroepiandrosterona (DHEA)

Função:
• Produção de androgénios insignificante no homem, quando
comparada com a secreção testicular;
• Importante fonte de androgénios no sexo feminino
(conversão periférica em T e E);
• Responsável pelos caracteres sexuais secundários
masculinos;

Regulação:
• Hormonal: ACTH (hipotálamo), CRH (hipófise), DHEA não
exerce controlo da regulação

Hormonal Responses to Exercise


Androgens

Physical Exercise
↑ CRH
↑ ACTH

Adrenal gland
↑ Cortisol
↑ Androgens

Exp Physiol 101.1 (2016) pp 168–175


Hormonal Responses to Exercise
Thyroid, calcitonin, and Parathyroid Hormone
Calcitonina

Produzida e secretada pela tiroide

Função:
- Osso: inibição da reabsorção óssea
• ↑ Atividade dos osteoblastos
• ↓ Atividade dos osteoclastos

Regulação:
- Humoral: [Ca2+] sangue

Secreção não é alterada pelo exercício físico

Hormonal Responses to Exercise


Thyroid, calcitonin, and Parathyroid Hormone
PTH
Produzida e secretada pela paratiroide

Função:
- Osso
• Reabsorção óssea
- Rim
• Síntese de Vitamina D
• Reabsorção de cálcio
• Reabsorção do fosfato
- Intestinos
• Reabsorção de cálcio

Regulação: Dados são insuficientes para tirar conclusões


- Humoral: [Ca2+] sangue sobre as respostas aos exercícios
- Hormonal: Vitamina D
Hormonal Adaptations to Training
60% VO2max
• Training programs are not usually deliberately designed to bring about
adaptations in the hormonal system.

• No research-based training principles have been established, and few


systematic attempts have been made to vary intensity, duration,
frequency, length of training period, and modality in large numbers of
subjects.

• The major hormones involved in fuel mobilization all show a


dampening effect as a result of exercise training -> represents a smaller
disruption of homeostasis than in the untrained state

• Trained individuals present increased levels of E, NE, and cortisol at the


end of incremental exercise (ability to do more high-intensity work)
Hormonal Adaptations to Training

Men Woman
Swimming Cross
Country
Skiing Swimming
Alpine Skiing

Power Lifting

Track and Field Track and Field

Power Lifting

Comparison of Growth hormone, IGF-I and collagen marker P-III-NP between sports (men on the left and women on the right). Each sport is represented by a numerical code and M=men and W= women: 1-Power Lifting (18 M and 1 W), 2-
Basketball (27 M and 14 W), 3-Football (Soccer;37 M), 4 Swimming (100 M and 91 W), 5-Marathon (1 W), 6-Canoeing (7 M and 1 W), 7-Rowing (36 M and 25 W), 8-Cross Country Skiing (8 m and 9 W), 9-Alpine Skiing (11 M and 12 W), 10-Weight
Lifting (10 M and 7 W), 11-Judo (26 M), 12-Bandy (19 M), 13-Ice Hockey (38 M), 14 Handball (23 M and 29 W) and 15-Track and Field (95 M and 49 W)

Hormonal Adaptations to Training

Adaptations Related to Muscle, Bone, and Adipose Tissue

Power Lifting

25.4 men with a testosterone value less than 10 nmol/l 4.8% athletes with testosterone level above 10 nmol/l

1-Power Lifting 5-Marathon 9-Alpine Skiing 13-Ice Hockey


2-Basketball 6-Canoeing 10-Weight Lifting 14 Handball
3-Football 7-Rowing 11-Judo 15-Track and Field
4 Swimming 8-Cross Country 12-Bandy
Skiing

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