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Table 4 The effects associated with NMDR relationships

From: Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

Organs and biological functions involved Observed effect (with number of associated NMDR relationships)a Substances involved
In vitrostudies In vivostudies
Hypothalamus Dopaminergic transmission (2) Aromatase activity in preoptic area (1) E2, octylphenol, diethylhexylphthalate (DEHP)
Pituitary gland Cell proliferation (1) GABAergic transmission (2) Calcium channel activity (2) Luteinizing hormone (LH) release (1) Prolactin release (12) Protein kinase modification (11) Follicle stimulating hormone (FSH) plasma level (1) LH plasma level (1) E2, phytoestrogens, BPA, alkylphenols, DES, organochlorines
Male reproductive system Testes Cell proliferation (1) Spermatid DNA breaks (1) Weight (2) Testosterone hydroxylase activity (4) E2, BPA, ethinyl estradiol
Epididymis,   Weight (2) E2, BPA
seminal vesicle,   Weight (1) BPA
preputial glands,   Weight (1) BPA
prostate Cell proliferation (1) Weight (5) E2, BPA, DES, dihydrotestosterone (DHT), alkylphenols
Female reproductive system Ovary Progesterone secretion (1) Testosterone secretion (1) Estradiol secretion (1) Transcriptional activity (1) PCBs, BPA
Uterus   Percentage of epithelial cells ERα + (1) Progesterone receptor expression (1) BPA
Breast   Modification of mammary epithelium and terminal end buds (15) E2, BPA, DES
Brain L-prostaglandin synthase activity (2) Calcium channel activity (2)   E2, pregnenolone, dehydroepiandrosterone (DHEA)
Cardiovascular system Heart Myocyte contractility (3)   E2, BPA
aortic smooth muscle Cell proliferation (1) Intracellular pH (1) Modification of protein kinase (2)   E2, BPA
Adrenal glands   Corticosterone plasma level (1) PCBs
Liver   Nuclear receptors expression (5) Transcriptional factors expression (4) BPA
Perinatal development   Age of puberty (1) Number of newborns (2) Weight of newborns (4) Anogenital distance (3) Sex-ratio (2) Newborn viability (3) Femur length (1) Growth (1) BPA, DEHP, DES, ethinyl estradiol, alkylphenols, methoxychlor, organochlorines
Behavior   Immobility period (1) Spatial memory (2) Temporal memory (2) Nocturnal activity (1) Territorial urine-marking (1) Sexual behavior (5) E2, 17α-estradiol, BPA, DES
Metabolism Lipids Adiponectin release (2) Adiponectin expression (1) Triglycerides levels (1) Lipogenesis gene expression (10) Cholesterol metabolism gene expression (4) BPA
Glucose   Glucose metabolism gene expression (2) Insulin levels (1) BPA
Immunity Mast cells degranulation (4) Rate of degranulated eosinophils and last cells (1) Macrophagic activity (1) Severity of allergic skin lesions (1) E2, organochlorines, alkylphenols, DEHP
Cancer   Tumor multiplicity (1) Tumor volume (1) Latency period for first tumor (1) Percentage of lung metastases (1) BPA
  1. aNumbers in parentheses represent the number of NMDR relationships associated with each corresponding effect.