Promotion of the Whitten effect in female mice by synthetic analogs of male urinary constituents.

Abstract

Two volatile constituents of male mouse urine, 2-(sec-butyl)-4,5-dihydrothiazole and dehydro-exobrevicomin, were synthesized and tested for their ability to induce estrous cycle in female mice (the Whitten effect). The suppression of ovarian cycling activity that resulted from grouping the females was abolished by exposure to normal male urine. The synthetic compounds, when added together in appropriate concentrations to the (previously inactive) urine of castrated males, or even to water, were found to be as effective as normal male urine. The action of the synthetic compounds appears attenuated for singly caged females.Stimuli from the social environment (primer pheromones) have been shown to influence both the frequency and composition of the estrous cycle in the mouse Mus musculus (1-4). Induction and synchronization of estrus among unisexually grouped females in the presence of a male [the Whitten effect (1)] and the male-induced failure of implantation and return to the estrous cycle [the Bruce effect (5)] are among the best known examples of male-to-female pheromonal effects in mice. Conversely, an all-female environment tdeds to suppress the estrous cycle: the effects of female grouping vary from an extension ofthe cycle length (6, 7), or prolongation of the quiescent phase of the estrous cycle (8), to induction of spontaneous pseudopregnancies (9,10). The pheromone(s) involved in the Whitten effect are excreted in the urine of intact adult males and their production is androgen-dependent (11). The active urinary substance(s) can elicit-a variety of endocrine responses in the female mice (12-14). These male-originated substances appear to act with a high degree of specificity in altering the secretory patterns of luteinizing hormone and prolactin and of the steroids whose secretion is regulated by these two tropic hormones (15). Regulation of the ovulatory function is among the most important reproductive consequences of these hormonal processes.Although it is becoming increasingly clear that both small and large molecules can act as mammalian pheromones (16-19), the results of Whitten et al. (20) and Gangrade and Dominic (21) support the idea that an airborne (volatile) signal is responsible for the Whitten effect. Analytical methods are now sufficiently advanced to elucidate structural features of the molecules causing various pheromonal effects.During comprehensive studies of the volatile components of urine of Mus musculus (22), two structurally unique substances have been found in association with the intact male: 2-(sec-butyl)-4,5-dihydrothiazole [2-(sec-butyl)thiazoline] and dehydro-exo-brevicomin. Through organic synthetic efforts (23), adequate quantities of these, substances are now available for biological testing. In parallel with possiblb pheromonal activities, the urinary concentration of dehydroexo-brevicomin is drastically reduced following castration, but testosterone supplementation restores it to the normal level (24).As we recently found that both dehydro-exo-brevicomin and...

Performing Vaginal Lavage, Crystal Violet Staining, and Vaginal Cytological Evaluation for Mouse Estrous Cycle Staging Identification

“…Variability in cycle length is also introduced with age and by housing differences within colonies (individual or group-housing) of females 7,[19][20][21] . Females housed in female-only colonies can cease cycling and enter a state of prolonged diestrus 18,22,23 although cycling can be re-instated by exposure to cages pretreated with male urine to elicit cycling 24,25 . Thus, to establish individual cycle lengths for a given mouse, it is recommended that the non-invasive assessments described here be performed daily, with care, until two complete cycles are observed.…”

In search of the chemical basis for MHC odourtypes

“…Some of the sources and chemical identity of these signals in mice have been studied, including MUPs (Hurst et al 2001;Chamero et al 2007), exocrine glands secreting peptides (Kimoto et al 2005), urinary signals of virus infection (Yamazaki et al 2002) and the animal's age (Osada et al 2003(Osada et al , 2008, and volatile semiochemicals that are involved in sexual communication (e.g. 2-secbutyl-4,5-dihydrothiazole, 3,4-dehydro-exo-brevicomin and methylthiomethanethiol; Jemiolo et al 1986;Lin et al 2005).…”

Stimulation of the GnRH Pulse Generator Activity by Continuous Exposure to the Male Pheromones in the Female Goat.

“…Although the reason is unclear, one possible explanation is that only volatile molecules could pass through the mesh of the mask and therefore the stimulation might have been insufficient as compared with the single application where the goat was allowed to not only smell but also taste the male goat hair. Mammalian pheromones were suggested to exhibit their effects more strongly if plural molecules could act cooperatively rather than as a single molecule [23][24][25][26]. Pheromones which induce the male effect in sheep, for example, are speculated to be a combination of two or more substances [27].…”