Cytochromes P450 in gibberellin biosynthesis

The gibberellins (GAs) are an important class of plant growth regulators that are active in many aspects of plant growth and development. GAs are synthesized by a complex pathway involving three enzyme classes spanning different subcellular compartments. One of these enzyme classes is the cytochrome P450s which catalyze a number of oxidation steps in the middle part of the pathway. Mutants in these cytochrome P450-mediated steps in a number of species have been crucial in isolating the genes encoding these enzymes and have also played an important role in understanding GA physiology. GAs are also synthesized by fungi, in a biosynthesis pathway largely catalyzed by cytochrome P450s. The fungal pathway appears to have evolved independently to that of higher plants.

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The shade avoidance syndrome: A non-Markovian stochastic growth model

Plants at high population density compete for light, showing a series of physiological responses known as the shade avoidance syndrome. These responses are controlled by the synthesis of the hormone auxin, which is regulated by two signals, an environmental one and an internal one. Considering that the auxin signal induces plant growth after a time lag, this work shows that plant growth can be modelled in terms of an energy-like function extremization, provided that the Markov property is not applied. The simulated height distributions are bimodal and right skewed, as in real community of plants. In the case of isolated plants, theoretical growth dynamics and speed correctly fit Arabidopsis thaliana experimental data reported in literature. Moreover, the growth dynamics of this model is shown to be consistent with the biomass production function of an independent model. These results suggest that memory effects play a non-negligible role in plant growth processes.     

A mathematical model of pregnancy recognition in mammals

In this paper we develop a mathematical model of the luteal phase of the reproductive cycle in mammals with the aim to generate a systems understanding of pregnancy recognition. Pregnancy recognition is initiated by the production of interferon tau (IFNτ) by the growing conceptus. This ensures that the maternal corpus luteum (CL) remains viable to secrete progesterone, which is critical for providing a uterine microenvironment suitable for embryonic growth. Our mathematical model describes the interactions among the CL, the reproductive hormones and the hormone receptors in the uterus. It also characterises the complex interactions amongst the uterine oestrogen, progesterone and oxytocin receptors that control the sensitivity of the uterus to oestrogen, progesterone and oxytocin, respectively. The model is represented by a dynamical system and exhibits qualitative features consistent with the known experimental results in sheep. A key factor identified was a time-dependent threshold for the IFNτ signal below which the presence of the embryo might not be recognised and thus pregnancy would likely fail. Furthermore, the model indicated that if the IFNτ signal is later than around day 13 of the cycle, then pregnancy will not be recognised irrespective of the IFNτ concentration. The thresholds in the concentration and time of the IFNτ signal is a screening mechanism whereby only embryos of sufficient quality are able to prevent luteolysis (i.e. regression of the CL). The effect of progesterone secretion rate from the CL on pregnancy recognition was investigated. The model suggests that if the secretion rate is low then the initiation of the IFNτ signal is delayed, which in turn compromises the likelihood of a pregnancy being recognised by the CL. Furthermore, pregnancy recognition does not occur below a critical threshold in the progesterone secretion rate. In summary, the model can be used to identify the most favourable conditions for pregnancy recognition.     

Inhibitory and disinhibitory effects of psychomotor stimulants and depressants on the sexual behavior of male and female rats

Drugs of abuse comprise several pharmacological classes, including psychomotor stimulants, such as amphetamine and cocaine, and CNS depressants, such as morphine and alcohol. Few studies have examined the effects of those drugs systematically on human sexual behavior, although substantial clinical and epidemiological literatures suggest that drugs in both classes either inhibit sexual responding or can be “prosexual” in certain situations, thereby increasing the potential of risky sexual activity and the spread of sexually transmitted diseases. This paper reviews original data in rats showing that both classes of drug inhibit or disinhibit sexual behavior depending on the animal's baseline level of sexual responding, hormonal status, whether the drug is given acutely or chronically, and whether the animal has learned to inhibit sexual responding toward nonreceptive partners or in the presence of conditioned olfactory cues that predict sexual nonreward.     

GPRC6A mediates the non-genomic effects of steroids

The identity of the putative G-protein coupled receptor (GPCR) that mediates the non-genomic effects of androgens is unknown. We present in vitro and in vivo evidence that the orphan GPRC6A receptor, a widely expressed calcium and amino acid sensing GPCR, transduces the non-genomic effects of testosterone and other steroids. Overexpression of GPRC6A imparts the ability of extracellular testosterone to illicit a rapid, non-genomic signaling response in HEK-293 cells lacking the androgen receptor. Conversely, testosterone-stimulated rapid signaling and phosphorylation of ERK is attenuated in bone marrow stromal cells derived from GPRC6A(-/-) mice and in 22Rv1 prostate cancer cells after siRNA-mediated knockdown of GPRC6A. Compared with wild-type controls, GPRC6A(-/-) null mice exhibit significantly less ERK activation and Egr-1 expression in both bone marrow and testis in response to pharmacological doses of testosterone in vivo. In addition, testosterone administration results in suppression of luteinizing hormone in wild-type male mice, but paradoxically stimulates serum luteinizing hormone levels in GPRC6A(-/-) null mice. These results suggest that GPRC6A is functionally important in regulating non-genomic effects of androgens in multiple tissues.