Structure-activity relationships of oral organosiloxanes on the male reproductive system

Bennett, D.R.; Gorzinski, S.J.; LeBeau, J.E.

doi:10.1016/0041-008x(72)90027-0

Cited by 39 publications

(12 citation statements)

References 7 publications

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“…Previous studies have reported the significant associations between the variation in genome size and life history 4, 5 , taxonomy 6 , evolutionary affiliation 7 and geographical distribution 8 . These associations were suggested to be determined by selective force 1, 3, 9 .…”

Section: Introductionmentioning

confidence: 99%

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants

Zheng

Wang

et al. 2017

Sci Rep

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The chloroplast genome originated from photosynthetic organisms and has retained the core genes that mainly encode components of photosynthesis. However, the causes of variations in chloroplast genome size in seed plants have only been thoroughly analyzed within small subsets of spermatophytes. In this study, we conducted the first comparative analysis on a large scale to examine the relationship between sequence characteristics and genome size in 272 seed plants based on cross-species and phylogenetic signal analysis. Our results showed that inverted repeat regions, large or small single copies, intergenic regions, and gene number can be attributed to the variations in chloroplast genome size among closely related species. However, chloroplast gene length underwent evolution affecting chloroplast genome size in seed plants irrespective of whether phylogenetic information was incorporated. Among chloroplast genes, atpA, accD and ycf1 account for 13% of the variation in genome size, and the average Ka/Ks values of homologous pairs of the three genes are larger than 1. The relationship between chloroplast genome size and gene length might be affected by selection during the evolution of spermatophytes. The variation in chloroplast genome size may influence energy generation and ecological strategy in seed plants.

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Section: Introductionmentioning

confidence: 99%

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants

Zheng

Wang

et al. 2017

Sci Rep

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“…However, the possibility of an additional direct antiandrogenic effect at the epididymis was also suggested [90]. Large doses caused adrenal hyperplasia, hepatomegaly, decreases in body weight and in serum levels of cholesterol, phospholipids and alkaline phosphatase [89,90]. These compounds were not evaluated in man.…”

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confidence: 92%

“…On the basis of concomitant dosage and some protective action of cysteine, leucine and lysine, it was suggested that the mechanism of antifertility action was mediated through interference with protein biosynthesis in the testis. These compounds were not tested in man.Organosiloxanes An organosiloxane (2,6-cis-diphenylhexamethylcyclo-tetrasiloxane; KABI 1774) ( Figure 7) was noted to be antispermatogenic in rats and mice (10 mg/kg daily), rabbits (2 mg/kg daily) and dogs (10 and 250 mg/kg daily) by the oral route [89][90][91]. The compound was more effective by oral than the subcutaneous or intraperitoneal routes of administration.…”

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confidence: 97%

Non-steroidal interference with male fertility

Vickery¹

1986

Adv Contracept

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IntroductionThe male gamete has long been thought to be the most vulnerable point at which to interfere with fertility, particularly when this could be accomplished noninvasively at the time of transfer from male to female reproductive tracts. Thus the earliest attempts to interfere with male fertility date back to Roman times [1]. They were mechanical in nature and depended upon prevention of intromission (infibulation) or use of a barrier (condom). Also from the beginnings of recorded history, materials have been inserted into the vagina which interact with spermatozoa to prevent fertilization. Early materials were employed empirically and consisted of acidic or sticky materials [2,3]. Early frank spermicidal materials included quinine and mercurials [4,5].A milestone in the development of spermicides was the discovery in the early 1950s of the efficacy of the detergents typified by nonoxynol-9 [6]. More potent surfactants have been identified from time to time [7]. In the carefully monitored, well-motivated small-scale clinical trials these vaginal spermicides can achieve failure rates as low as 0.3 per 100 women years, essentially equivalent to the oral contraceptives for women [8][9][10][11]. Unfortunately, in widespread use, failure rates are much higher and retrospective surveys have shown up to 40% of users to become pregnant within 1 year [12][13][14][15]. With the exception of the animal studies reported on an imidazole with some additional loci of action [16--18] and some acrosin and hyaluronidase inhibitors [19--21], no noteworthy research has appeared in this area recently.It is probable that attempting to nullify very large numbers of normal motile spermatozoa within the female tract and within the anatomical and time constraints involved is doomed to failure. A better approach to male contraception with lesser constraints would likely be through administration of agents directly to the male. The present review addresses the varied history of this approach as it applies to non-steroidal materials. Advances in (i) Pituitary inhibitionHormonally active agents The earliest recorded studies on control of male fertility by chemical means administered to the male capitalized upon the observation that administration of low doses of testosterone to male rats was antispermatogenic [22]. As we now know, this reflected sufficient circulating androgen to cause feedback inhibition of gonadotropin release but insufficient intratesticular androgen levels to maintain spermatogenesis directly [23][24][25]. Studies in men with testosterone or its esters, however, never consistently achieved azoospermia or protection from pregnancy, except at dose levels expected to change lipoprotein formation and/or blood cell formation [26--28]. The long history of attempts to use steroids as indirect regulators of spermatogenesis is outside the scope of this review and is described by Dr Nieschlag in his review paper [29].From time to time non-steroidal structures with hormonal activity have been described ( Figure 1) and used ...

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“…Thus, cyclosiloxanes are a new and novel class of structures mimicking some of the physical and biological properties of hormonal steroids. Cyclic 2,6-cis-[(PhMeSiO)z(MezSiO)z] is an orally active moderate estrogen (Hayden & Barlow 1972) with postcoital antifertility activity in the rat attributable to ovum destruction and accelerated tuba1 transport (Le Vier & Jankowiak 1972a) Oral administration of this cyclosiloxane suppresses testicular function and accessory tissue weights in the rabbit, rat and mouse (Bennett et al 1972). Other studies in the male rat have shown that this cyclosiloxane is an antigonadotropin consistent with its estrogenicity (Le Vier & Jankowiak 1972b).…”

mentioning

confidence: 99%

The Antigonadotropic Activity of an Organosiloxane in the Male Rat: 2,6‐cis‐Diphenylhexamethylcyclotetrasiloxane

1975

Acta Pharmacologica et Toxicologica

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An organosilicon compound, 2,615s -diphenylhexamethylcyclotetrasiloxane, was investigated as an orally active estrogenic antigonadotropin in the male rat and compared to subcutaneously administered estradiol benzoate. The cyclosiloxane lowered serum LH and FSH in association with sex accessory tissue atrophy. Serum LH declined to 50 % of the control level within 5 hrs. of a single dose of the cyclosiloxane; FSH declined more slowly. Gonadotropin levels were further decreased to 15-20 % of the control level after one week of treatment. A direct anterior pituitary block was demonstrated in LFW challenged animals 8 hrs. after a single dose of the cyclosiloxane; estradiol blocked the pituitary as early as 1 hr. after estrogen administration. The cyclosiloxane decreased available releasing hormone activity at 24 hrs. This action was associated with an increase in the median eminence content of dopamine and an in vivo decrease in the rate of synthesis of dopamine from 14C-tyrosine. Estradiol had a similar but weaker effect. On the basis of these data it was postulated that this unusual nonsteroid structure exerts its effects at the level of the anterior pituitary and on the hypothalamus.

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Structure-activity relationships of oral organosiloxanes on the male reproductive system

Cited by 39 publications

References 7 publications

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants

Non-steroidal interference with male fertility

The Antigonadotropic Activity of an Organosiloxane in the Male Rat: 2,6‐cis‐Diphenylhexamethylcyclotetrasiloxane

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