Juvenile Hormone Biosynthesis in Insects: What Is New, What Do We Know, and What Questions Remain?

Abstract

Our understanding of JH biosynthesis has significantly changed in the last years. In this review I would like to discuss the following topics: (1) the progresses in understanding the JH biosynthesis pathway. Access to genome sequences has facilitated the identification of all the genes encoding biosynthetic enzymes and the completion of comprehensive transcriptional studies, as well as the expression and characterization of recombinant enzymes. Now the existence of different flux directionalites, feed-back loops and pathway branching points in the JH biosynthesis pathways can be explored; (2) the new concepts in the modulation of JH synthesis by allatoregulators. The list of putative JH modulators is increasing. I will discuss their possible role during the different physiological states of the CA; (3) the new theoretical and physiological frameworks for JH synthesis analysis. I will discuss the bases of the flux model for JH biosynthesis. JH plays multiple roles in the control of ovary development in female mosquitoes; therefore, the CA presents different physiological states, where JH synthesis is altered by gating the flux at distinctive points in the pathway; (4) in the final section I will identify new challenges and future directions on JH synthesis research.

Figure 1

JH biosynthesis pathway. The biosynthesis of JH III involves 13 enzymatic reactions that can be conventionally divided into early (MVAP) and late (JH-branch) steps. Metabolites are shown in bold and enzymes in italic. Chemical structures are in [4].

Figure 2

JH biosynthesis rates and ovarian development in female mosquitoes. Top panel: representative images of the progression of ovary development from emergence to 24 h after blood feeding. The inset in 96 h shows the lipid content of follicles from females fed 3% sugar (top) and 20% sugar (bottom). Colors for the panels match the colors for the nutrition-dependent physiological states of the CA shown in the panel below. Bottom panel: JH biosynthesis by CA dissected from pupa, sugar-fed, and blood-fed adult females. Hours represent times before (pupa) and after adult emergence (sugar-fed), or after blood feeding (BF). Y-axis: JH biosynthesis expressed as fmol/h. Bars represent the means ± SEM of three independent replicates of three groups of 3 CA. Colors represent the four distinct CA physiological phases identified: inactive or low activity CA (blue), active CA (black), modulated CA (green), and suppressed CA (red), from [12].

Figure 3

Starvation effects on insulin signaling components and JH synthesis in the CA of mosquitoes. This scheme summarizes starvation-related changes of insulin/TOR pathway components and JH synthesis. Molecules in red color are downregulated (↓), while those in green are upregulated (↑). Phosphoinositide 3-kinase (PI3K) and TOR are involved in the transduction of insulin signaling in the CA [13]. A starvation-dependent decrease of insulin results in an increase of FOXO signaling that promotes activation of transcription of insulin receptor (INSr) and 4E-binding protein (4EBP). Transcripts levels for FOXO increase and mRNAs for JHAMT and TOR decrease. JH synthesis decreases, while increases of 4EBP inhibit translation and increases of INSr enhance insulin sensitivity, from [23].

Figure 4

Effect of modulators on JH biosynthesis in female mosquitoes. Schematic representation of some of the tissues and molecules involved in JH biosynthesis regulation in mosquitoes. PG: prothoracic gland. OV: ovaries. CC: corpora cardiaca. CA: corpora allata. ETH: ecdysis triggering hormone. AST-C: allatostatin-C. AT: allatotropin. INS: insulin. 20E: 20 hydroxyecdysone. R: receptor. JH: juvenile hormone. Green arrow: stimulation. Red arrow: inhibition. Black arrow: modulation.

Figure 5

A schematic representation of a model for the control of the flux of precursors in the JH biosynthetic pathway. Precursor pools (S2, S3, etc.) are represented by circles and connected by arrows (MVA: mevalonic acid, 5P-MVA: mevalonate 5-phosphate). E: enzymes are followed by a number that refers to the position in the pathway (E3 = MK: mevalonate kinase). Regulatory factors might be affecting both precursor pool sizes and enzymatic activities (e.g., AST-C: allatostatin-C). JH: juvenile hormone, from [6].

Figure 6

Heat map representation of changes in JH biosynthetic enzyme mRNAs and activities in CA extracts. (a) Changes in mRNAs encoding JH biosynthetic enzymes. (b) Changes in activities of JH biosynthetic enzymes in CA extracts. Top: physiological stages are described as hours relative to adult emergence (0 h) or blood feeding (BF). Right side: enzyme names abbreviations: Acetoacetyl-CoA thiolase: thiolase; HMG-CoA synthase: HMGS; HMG-CoA reductase: HMGR; mevalonate kinase: MK; phosphomevalonate kinase: PMK; diphosphomevalonate decarboxylase: PPM-Dec; IPP isomerase: IPPI; FPP synthase: FPPS; farnesyl pyrophosphatase: FPPase; farnesol dehydrogenase: FOL-SDR; farnesal dehydrogenase: FALDH; juvenile hormone acid methyltransferase: JHAMT; and methyl farnesoate epoxidase: EPOX. Colors from white to red represent increases of transcript levels or enzymatic activities as percentages of the maximum value, from [12].

Figure 7

Schematic representation of the distinct four CA physiological conditions in reproductive female mosquitoes. The four CA phases and corresponding stages are as follows: inactive (early pupae), active (12–24 h sugar-fed females), modulated (48–96 h sugar-fed females), and suppressed (24 h blood-fed females). JH synthesis: the color and direction of the arrows reflect the following: low levels (arrows down and red), high levels (arrows up and black), or variable levels (arrow up and down). Changes in transcripts, activities, and metabolites are as follows: the direction of the arrows reflects the trend of the changes (increases: up and decreases: down); the size of the arrow reflects the magnitude of the changes, limiting factor: hypothetical critical factor limiting CA activity, from [12].