Phylogeny and Ontogeny of Hormone Receptors: The Selection Theory of Receptor Formation and Hormonal Imprinting

Csaba, G.

doi:10.1111/j.1469-185x.1980.tb00687.x

Cited by 305 publications

(115 citation statements)

References 57 publications

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“…The term 'hormonal imprinting' covers experimental observations, which suggest that influences acting on hormone receptors during a critical period of maturation play a decisive role in the development and responsiveness later in life (35). Thus, a single perinatal treatment with the synthetic estrogens DES and allylestrenol has been shown to give rise to a lasting decrease in the number of rat uterine estrogen receptors (36) and to a lasting change in the responsiveness to testosterone by the microsomal enzyme activity of rat liver (37).…”

Section: Prepubertal Boysmentioning

confidence: 99%

Exposure to exogenous estrogens in food: possible impact on human development and health

1999

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There has been increasing concern about the impact of environmental compounds with hormone-like action on human development and reproductive health over the past decades. An alternative but neglected source of hormone action that may be considered in this connection is hormone residues in meat from husbandry animals treated with sex steroid hormones for growth promotion. Treatment of cattle with naturally occurring or synthetic sex hormones may enhance lean muscle growth and improve feed efficiency and is therefore a very cost effective procedure for cattle producers who have used it for decades in some Western countries, including the USA and Canada. The Joint Food and Agricultural Organisation/World Health Organisation (FAO/WHO) expert committee on food additives (JECFA) and the US Food and Drug Administration (FDA) considered, in 1988, that the residues found in meat from treated animals were safe for the consumers.We have re-evaluated the JECFA conclusions regarding the safety of estradiol residues in meat in the light of recent scientific data, with special emphasis on estradiol levels in prepubertal children. These levels are needed for estimates of the normal daily production rates of estradiol in children, who may be particularly sensitive to low levels of estradiol.In our opinion, the conclusions by JECFA concerning the safety of hormone residues in meat seem to be based on uncertain assumptions and inadequate scientific data. Our concerns can be summarized as follows. 1) The data on residue levels in meat were based on studies performed in the 1970 s and 1980 s using radioimmunoassay (RIA) methods available at the time. The sensitivity of the methods was generally inadequate to measure precisely the low levels found in animal tissues, and considerable variation between different RIA methods for measuring steroids exists. Therefore the reported residue levels may be subject to considerable uncertainty. 2) Only limited information on the levels of the various metabolites of the steroids was given despite the fact that metabolites also may have biological activity. 3) Reliable data on daily production rates of steroid hormones were and are still lacking in healthy prepubertal children. This lack is crucial as previous guidelines regarding acceptable levels of steroid residues in edible animal tissues have been based on very questionable estimates of production rates in children. Thus, even today the US FDA bases its guidelines on the presumably highly overestimated production rates in prepubertal children given in the JECFA 1988 report. 4) The possible biological significance of very low levels of estradiol is neglected.In conclusion, based on our current knowledge possible adverse effects on human health by consumption of meat from hormone-treated animals cannot be excluded.

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Section: Prepubertal Boysmentioning

confidence: 99%

Exposure to exogenous estrogens in food: possible impact on human development and health

1999

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“…Although mammalian steroid receptors are mostly intracellular [ 14,29-3 11, increasing evidence suggests that they may also be present in the membrane [26,27]. In fact, soluble receptors in eukaryotes may have arisen from the internalization of membrane receptors of the type found in unicellular organisms, rather than by a chance encounter between intracellular proteins and loitering steroids [37]. molecular cloning of plant receptors, followed by sequence alignment, may reveal that plants are very much a part of the phylogeneti~ tree where steroid receptors probably evolved by successive shuffling of a primordial ancestor gene to increase sensitivity of transactivation pathways [38].…”

Section: Future Perspectivesmentioning

confidence: 99%

Receptors for mammalian steroid hormones in microbes and plants

Agarwal

1993

FEBS Letters

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Steroids are of universal occurrence, present variously as cell wall constituents and bioregulators. A number of bacteria, fungi, and photosynthetic vascular plants synthesize steroids that are honnonally active in the animal world. The cellular effect of such steroids in microbes and plants appears by and large to be comparable to that in mammals. Available evidence suggests that steroid action in botanical phyla is mediated via receptors organized in a manner similar to that seen in animals. Therefore, the ancestry of ligand induced transactivation via zinc finger proteins appears to date farther back than the early Cambrian burst of metazoan evolution 500 million years ago.Microbe; Plant; Steroid; Hormone; Receptor 1. STEROID DISTRIBUTION AND SYNTHESIS formed to steroids hormonally active in animals and plants [6-81. Receptor mediated control of transcription by steroid hormones (Fig. 1) is a subject of much contemporary interest in mammalian biology. In microbes and plants, the evidence for distribution, synthesis, and physiological action, of steroids has remained rather circumscribed, and sometimes even contradictory. This minireview traces the role played by steroids as messengers at various levels of evolution, as a prelude to understanding receptor origin for further experimental inquiry.Cholesterol is the common starting material in animals for P450 mediated synthesis of all classes of steroid hormones [9]. Plant species have been variously shown to contain glucocorticoids (cortisol), mineralocorticoids (deoxycorticosterone), progestins (progesterone), androgens (testosterone), estrogens (estradiol and estrone) and even the insect moulting hormone ecdysone [2,[5][6][7]10,, as shown in Table I.Life on earth is believed to have originated some 4 billion years ago from about 30 biologically useful precursors, formed from simple inorganic matter under the influence of the cosmic energy reaching our planet. Steroids are of universal occurrence, present in the cell variously as membrane constituents, chemical messengers, vitamins, cytotoxins, and hormones [1,2]. CELLULAR FUNCTION OF STEROIDSWhereas prokaryotic transformation of steroids is rich in diversity [3], the synthesis of sterols follows two major routes in higher organisms [4]. Squalene 2,3-oxide, formed from acetate via common pathways, is cyclized either to lanosterol in non-photosynthetic eukaryotes (fungi, animals), or to cycloartenol in photosynthetic phyla [4]. Insects transform steroids and ster01s ingested during feeding [2]. Plant sterols, saponins, cardiac glycosides, and alkaloids are of much biomedical value, but have no demonstrated counterparts or hormonal role in mammals [5]. Several bacterial and plant species synthesize cholesterol which is then transEarlier studies had shown that bacteria, mycoplasma (PPLO), and fungi respond to sterols and steroids in bewildering ways, ranging from vitamin-like to antimicrobial [7]. Mammalian gonadal hormones generally inhibit the growth of bacteria, in particular the Grampositive organisms [7,11]....

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“…A születéssel azonban a magzati endokrin rendszernek is át kell állnia a saját vezérlésre, tehát a saját maga által termelt hormonokat kell felismernie az újszülött receptorainak. Az átállás a perinatalis kritikus periódus-ban történik meg, amikor végbemegy a hormonális imprinting, amely életre szólóan határozza meg a receptor és a hormon további viszonyát, elsősorban a receptor kötési kapacitását [1]. Ez egy minőségileg és mennyisé-gileg pontosan beállított mechanizmus, amelyet azonban ilyenkor megzavarhat az idegen, de kapcsolódni ké-pes molekulák jelenléte, így hibás hormonális imprinting jön létre akár egyetlen receptor-hormon kapcsolat által.…”

Section: A Receptor-hormon Kapcsolatunclassified

A hormonális rendszer válsága: az endokrin diszruptorok egészségügyi hatásai

Csaba

2017

Orvosi Hetilap

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Az endokrin diszruptorok a környezetből az állati (emberi) szervezetbe jutó olyan természetes vagy mesterséges molekulák, amelyek hormonreceptorokhoz kapcsolódva serkentik vagy gátolják adott sejtek tevékenységét, hormonok vagy receptorok előállítását, illetve transzportját. Ha kapcsolódásuk valamely kritikus periódusban történik, hibás hormonális imprintinget hoznak létre életre szóló következményekkel, mint hormonbefolyásolt sejtműködések megváltozása, betegségekre való hajlam manifesztálódása vagy betegségek megjelenése, ezért orvosi-egészségügyi jelentőségük van. Az endokrin diszruptorok száma nagy és éppúgy, mint felhasználásra kerülő mennyiségük, növekszik, ezáltal számos, felnőttkorban megjelenő kórkép (például daganat) visszavezethető perinatalis kori endokrin diszruptorártalmakra. Tartós hatásuk alapvető emberi jellegzetességek (például menarche időpontja) megváltozásához vezet. Az A-és D-vitamin is hormon (exohormon) és kívülről bejutva a szervezetbe endokrin diszruptorok lehetnek. Az endokrin diszruptorok által kiváltott imprinting az utódgenerációkra epigenetikusan átadódik, így befolyásolhatja az utódok gyógyszerérzékenységét is. Ha az epigenetikus öröklődés tartóssá válik, annak humánevolúciós jelentősége is lehet.

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Phylogeny and Ontogeny of Hormone Receptors: The Selection Theory of Receptor Formation and Hormonal Imprinting

Cited by 305 publications

References 57 publications

Exposure to exogenous estrogens in food: possible impact on human development and health

Exposure to exogenous estrogens in food: possible impact on human development and health

Receptors for mammalian steroid hormones in microbes and plants

A hormonális rendszer válsága: az endokrin diszruptorok egészségügyi hatásai

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