Retinoids and pattern formation in a hydroid

Development ◽  
1984 ◽  
Vol 81 (1) ◽  
pp. 253-271
Author(s):  
W. A. Müller
Keyword(s):  
Retinoic Acid ◽  
Prolonged Treatment ◽  
Low Doses ◽  
Response Curves ◽  
Head Formation ◽  
Pulse Type ◽  
Head Activator ◽  
High Doses ◽  
Pattern Specification ◽  
Hydroid Polyps

The retinoids (retinol, retinal, retinoic acid) cause alterations in the pattern of limb elements in vertebrates (Summerbell & Harvey, 1983). As shown here, retinoids also influence pattern specification in hydroid polyps (Hydractinia echinata) in a way suggesting interference with the generation and transmission of signals responsible for the dimension and spacing of structures. A pulse-type application of low doses (e.g. retinoic acid 10-6 to 10-10 M, 4 h) causes metamorphosing primary polyps to develop more tentacles but fewer stolons per unit circumference, to shorten the length of the hydranth while the stolon elongates, and to bud secondary hydranths at high frequency 2–3 days after treatment (Fig. 3). Dose-response curves display optimum peaks. It is argued that the increase in budding rate is due to a reduction of the range of spacing signals emitted by the primary hydranth. In regenerating hydranths, low doses (10−10 to 10−9M) improve the rate of head formation, whilst medium doses (10−8 to 10−6M) result in more tentacles being regenerated. However, prolonged treatment with high doses (10−6 to 10−5 M) causes the animals to reduce all head structures and to transform eventually into stolons, in contravention of the rule of distal transformation that they normally obey (Fig. 8). The effects of the retinoids are counteracted by a putative morphogen, the endogenous inhibitor isolated from Hydra by Berking (1977). The Hydra-derived ‘head-activator’ displayed no stimulating effect on the number of tentacles and buds formed.

Retinoic acid and pattern formation in the developing chick wing: SEM and quantitative studies of early effects on the apical ectodermal ridge and bud outgrowth

Development ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 139-169
Author(s):  
J. Lee ◽  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Local Application ◽  
Local Source ◽  
Local Concentration ◽  
Low Doses ◽  
Response Curves ◽  
Wing Patterns ◽  
Skeletal Pattern ◽  
High Doses ◽  
Dose Dependent

When retinoic acid is locally applied to the anterior margin of developing chick wing buds on ion-exchange beads, dose-dependent changes in the skeletal pattern result. At low doses, additional digits develop. At high doses, there is thinning of the symmetrical wing. Local application of retinoic acid to the apex of the bud also leads to pattern changes, but in contrast normal wing patterns are almost always obtained following application posteriorly. These effects are manifest at 6–7 days after the operation although only a brief exposure (14–20 h) to retinoic acid is required. Therefore the morphology of wing buds was studied at shorter times after the start of treatment. The local application of retinoic acid to the wing bud margin leads to changes in extent of the apical ridge that can be detected at 24 h after application. The behaviour of the apical ridge with varying doses and positions of retinoic acid application has been analysed quantitatively and dose response curves obtained. At low doses of retinoic acid, the length of the apical ridge increases or remains constant, but then progressively decreases with higher doses. The progressive obliteration of the ridge starts first near the bead and then involves more distant parts of the bud. Thus the region of the ridge affected depends on the position at which the retinoic acid is applied. We propose that these effects on the apical ridge reflect dose-dependent responses to the local concentration of retinoic acid that varies with distance from the source. At high doses, the apical ridge disappears but at low doses it is maintained. Since grafts of polarizing region tissue also have a graded effect on ridge morphology, a possible interpretation of the retinoic acid effects is that tissue adjacent to the source is converted into polarizing region tissue. Alternatively, retinoic acid may act directly on the ridge cells. The changes in the extent of the apical ridge produced by retinoic acid lead to different forms of bud outgrowth. The form of the outgrowth depends on the dose of retinoic acid, the position of application and the interaction between the effects of the local source of retinoic acid and those of the polarizing region of the host bud. These considerations give some insights into why anterior application of retinoic acid leads to the development of additional digits whereas posterior application generally gives normal wings.

Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response

2005 ◽  
Vol 24 (9) ◽  
pp. 431-437 ◽  
Author(s):  
Lennart Weltje ◽  
Frederick S vom Saal ◽  
Jörg Oehlmann
Keyword(s):  
Risk Assessment ◽  
Adaptive Response ◽  
Low Dose ◽  
Threshold Model ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Chemicals ◽  
Low Doses ◽  
Response Curves ◽  
Endocrine Disrupting ◽  
High Doses

We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.

scholarly journals The effect of local application of retinoic acid to the anterior margin of the developing chick limb

Development ◽  
1983 ◽  
Vol 78 (1) ◽  
pp. 269-289
Author(s):  
Dennis Summerbell
Keyword(s):  
Retinoic Acid ◽  
Limb Development ◽  
Anterior Margin ◽  
Mirror Image ◽  
Limb Bud ◽  
Local Application ◽  
Low Doses ◽  
Full Dose ◽  
Early Stages ◽  
High Doses

Local application of retinoic acid to the chick limb bud produces effects that are dose and/or stage dependent. Low doses and/or old stages tend to give normal limbs or perhaps one or two supernumerary digits of a more anterior character. Medium doses and/or intermediate stages tend to give full mirror-image supernumeraries with two or even three extra digits including particularly digits of a posterior character. High doses and/or early stages give limbs in which supernumerary digits fail to form or are lost, and in which even host skeletal elements are missing or reduced. The effects are graded over the full dose and/or stage range. Various explanations are discussed in the context of the current hypotheses of limb development. We conclude that one should not necessarily interpret the results as evidence that retinoids normally play a part in the control of development or regeneration.

ANTAGONISTIC ACTION OF NORETHYNODREL ON THE TESTOSTERONE-DEPENDENT PROCESS OF FRUCTOSE FORMATION IN MOUSE SEX ACCESSORY ORGANS

1966 ◽  
Vol 51 (2) ◽  
pp. 224-230 ◽  
Author(s):  
John A. Thomas ◽  
Edward T. Knych
Keyword(s):  
Antagonistic Activity ◽  
Low Doses ◽  
Antagonistic Action ◽  
Dependent Process ◽  
High Doses

ABSTRACT Norethynodrel antagonized the fructose stimulating effects of exogenous testosterone in sex accessory organs of castrate mice. It was antiandrogenic at both low doses (50 μg) and high doses (400 μg) of testosterone. Norethindrone and ethisterone suppressed fructose formation in the testosterone-treated castrate mouse, but not as effectively as norethynodrel. Norethandrolone exerted no antagonistic activity.

EFFECT OF HIGH DOSES OF OESTROGEN AND PROGESTERONE ON THE NORADRENALINE CONTENT OF THE SHORT ADRENERGIC NEURONS INNERVATING THE MALE GENITAL TRACT OF THE RAT

1970 ◽  
Vol 64 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Ch. Owman ◽  
N.-O. Sjöberg ◽  
N. O. Sjöstrand ◽  
G. Swedin
Keyword(s):  
Genital Tract ◽  
Reproductive Tract ◽  
Female Genital Tract ◽  
Total Content ◽  
Prolonged Treatment ◽  
Noradrenaline Content ◽  
Adrenergic Neurons ◽  
Short Adrenergic Neurons ◽  
High Doses ◽  
Male Genital

ABSTRACT The effect of prolonged treatment with high doses of oestrogen and/or progesterone on the amount of adrenergic transmitter in the short adrenergic neurons of the male reproductive tract of castrated rats has been studied by chemical determinations and histochemical demonstration of noradrenaline. Oestrogen, progesterone, or a combination of both, had no overt effect on the total content or on the concentration of noradrenaline in the male genital organs. The results are discussed in the light of recent findings that the content of the noradrenaline transmitter in the short adrenergic neurons to the female genital tract is markedly influenced by these female sex hormones.

scholarly journals Antifertility Actions of a-Chlorohydrin in the Male

1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones
Keyword(s):  
Male Fertility ◽  
Human Sperm ◽  
Male Rat ◽  
Low Doses ◽  
Dose Regime ◽  
Male Contraceptive ◽  
The Past ◽  
High Doses ◽  
Species Specific ◽  
Daily Oral Administration

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, oc-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster,rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of oc-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic oc-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as oc-chlorohydrin; this article reviews the progress that has been achieved with oc-chlorohydrin during the past six years.

Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 691-705 ◽  
Author(s):  
C. Tickle ◽  
A. Crawley ◽  
J. Farrar
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Time Course ◽  
Apical Ectodermal Ridge ◽  
Threshold Response ◽  
Epithelial Morphology ◽  
Early Effects ◽  
High Doses ◽  
Columnar Cells ◽  
Dose Dependent

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

Gastrointestinal motor effects of erythromycin

1990 ◽  
Vol 259 (3) ◽  
pp. G355-G363 ◽  
Author(s):  
M. F. Otterson ◽  
S. K. Sarna
Keyword(s):  
Small Intestine ◽  
Cycle Length ◽  
Amplitude Ratio ◽  
Contractile Activity ◽  
Low Doses ◽  
Control Activity ◽  
Distal Small Intestine ◽  
Gastrointestinal Motor ◽  
High Doses ◽  
Motor Effects

We studied the small intestinal motor effects of oral and intravenous (iv) erythromycin in 10 conscious dogs. After control recordings with placebo, oral or iv erythromycin was given at 40% of the migrating motor complex (MMC) cycle. Recordings were made after administration until normal contractile activity had returned or 12 h postdrug administration. Low doses initiated a premature MMC. High doses, however, prolonged the MMC cycle length. Erythromycin reduced the MMC propagation velocity at all doses. Both oral and iv erythromycin induced amyogenesia. During this pattern, electrical control activity was obliterated in the proximal and destabilized in the distal small intestine. Erythromycin also increased the incidence of retrograde giant contractions (RGCs) and vomiting. These effects occurred within the first 2 h after oral and within the first 30 min after iv administration. The incidence of giant migrating contractions (GMCs) increased significantly from 5 to 12 h but not from 0 to 5 h after administration. The distance of origination of GMCs from the ileocolonic junction was significantly increased from 5 to 12 h. The amplitude ratio, duration, and velocity of migration of GMCs induced after erythromycin were similar to control values. Clusters of coordinated antral and duodenal contractions also occurred early after administration. Our findings suggest that erythromycin has multiple motor effects on the stomach and small intestine. Diarrhea, abdominal cramping, and vomiting associated with erythromycin may be related to increased incidence of GMCs and RGCs. Erythromycin has a biphasic effect on MMC cycle length, initiating premature MMCs at low doses and prolonging their cycle length at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

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