The dare gene: steroid hormone production, olfactory behavior, and neural degeneration in Drosophila

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4591-4602 ◽  
Author(s):  
M.R. Freeman ◽  
A. Dobritsa ◽  
P. Gaines ◽  
W.A. Segraves ◽  
J.R. Carlson
Keyword(s):  
Nervous System ◽  
Steroid Hormones ◽  
Steroid Hormone ◽  
Larval Instar ◽  
Hormone Production ◽  
Ring Gland ◽  
Olfactory Stimuli ◽  
Steroid Hormone Signaling ◽  
Adrenodoxin Reductase ◽  
Strength Result

Steroid hormones mediate a wide variety of developmental and physiological events in insects, yet little is known about the genetics of insect steroid hormone biosynthesis. Here we describe the Drosophila dare gene, which encodes adrenodoxin reductase (AR). In mammals, AR plays a key role in the synthesis of all steroid hormones. Null mutants of dare undergo developmental arrest during the second larval instar or at the second larval molt, and dare mutants of intermediate severity are delayed in pupariation. These defects are rescued to a high degree by feeding mutant larvae the insect steroid hormone 20-hydroxyecdysone. These data, together with the abundant expression of dare in the two principal steroid biosynthetic tissues, the ring gland and the ovary, argue strongly for a role of dare in steroid hormone production. dare is the first Drosophila gene shown to encode a defined component of the steroid hormone biosynthetic cascade and therefore provides a new tool for the analysis of steroid hormone function. We have explored its role in the adult nervous system and found two striking phenotypes not previously described in mutants affected in steroid hormone signaling. First, we show that mild reductions of dare expression cause abnormal behavioral responses to olfactory stimuli, indicating a requirement for dare in sensory behavior. Then we show that dare mutations of intermediate strength result in rapid, widespread degeneration of the adult nervous system.

scholarly journals Irisin deletion induces a decrease in growth and fertility in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yunyao Luo ◽  
Xiaoyong Qiao ◽  
Yaxian Ma ◽  
Hongxia Deng ◽  
Charles C. Xu ◽  
...  
Keyword(s):  
Body Weight ◽  
Steroid Hormones ◽  
Energy Homeostasis ◽  
Steroid Hormone ◽  
Mutant Mice ◽  
Sequencing Analysis ◽  
Hormone Production ◽  
Poor Growth ◽  
Reduced Body ◽  
Deficient Mice

Abstract Background Irisin, which is cleaved from fibronectin type III domain-containing protein 5 (Fndc5), plays an important role in energy homeostasis. The link between energy metabolism and reproduction is well known. However, the biological actions of irisin in reproduction remain largely unexplored. Methods In this study, we generated Fndc5 gene mutation to create irisin deficient mice. Female wild-type (WT) and Fndc5 mutant mice were fed with standard chow for 48 weeks. Firstly, the survival rate, body weight and fertility were described in mice. Secondly, the levels of steroid hormones in serum were measured by ELISA, and the estrus cycle and the appearance of follicles were determined by vaginal smears and ovarian continuous sections. Thirdly, mRNA-sequencing analysis was used to compare gene expression between the ovaries of Fndc5 mutant mice and those of WT mice. Finally, the effects of exogenous irisin on steroid hormone production was investigated in KGN cells. Results The mice lacking irisin presented increased mortality, reduced body weight and poor fertility. Analysis of sex hormones showed decreased levels of estradiol, follicle-stimulating hormone and luteinizing hormone, and elevated progesterone levels in Fndc5 mutant mice. Irisin deficiency in mice was associated with irregular estrus, reduced ratio of antral follicles. The expressions of Akr1c18, Mamld1, and Cyp19a1, which are involved in the synthesis of steroid hormones, were reduced in the ovaries of mutant mice. Exogenous irisin could promote the expression of Akr1c18, Mamld1, and Cyp19a1 in KGN cells, stimulating estradiol production and inhibiting progesterone secretion. Conclusions Irisin deficiency was related to disordered endocrinology metabolism in mice. The irisin deficient mice showed poor growth and development, and decreased fertility. Irisin likely have effects on the expressions of Akr1c18, Mamld1 and Cyp19a1 in ovary, regulating the steroid hormone production. This study provides novel insights into the potential role of irisin in mammalian growth and reproduction.

scholarly journals Functional Roles of Protein Kinase A (PKA) and Exchange Protein Directly Activated by 3′,5′-Cyclic Adenosine 5′-Monophosphate (cAMP) 2 (EPAC2) in cAMP-Mediated Actions in Adrenocortical Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2151-2161 ◽  
Author(s):  
Linda Aumo ◽  
Marte Rusten ◽  
Gunnar Mellgren ◽  
Marit Bakke ◽  
Aurélia E. Lewis
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Steroid Hormones ◽  
Steroid Hormone ◽  
Regulatory Protein ◽  
Adrenocortical Cancer ◽  
Hormone Production ◽  
Genes Encoding ◽  
And Migration ◽  
Kinase A

In the adrenal cortex, the biosynthesis of steroid hormones is controlled by the pituitary-derived hormone ACTH. The functions of ACTH are principally relayed by activating cAMP-dependent signaling pathways leading to the induction of genes encoding enzymes involved in the conversion of cholesterol to steroid hormones. Previously, protein kinase A (PKA) was thought to be the only direct effector of cAMP. However, the discovery of the cAMP sensors, exchange proteins directly activated by cAMP (EPAC1 and 2), has led to a reevaluation of this assumption. In the present study, we demonstrate the occurrence of the EPAC2 splicing variant EPAC2B in adrenocortical cancer cells. Immunocytochemistry demonstrated that EPAC2B is localized predominantly in the nucleus. EPAC2B is functional because it activates Rap1 in these cells. Using the cAMP analogs 8-p-chlorophenylthio-2′-O-methyl-cAMP and N6-benzoyl-cAMP, which specifically activate EPAC1/2 and PKA, respectively, we evaluated the contribution of these factors in steroid hormone production, cell morphology, actin reorganization, and migration. We demonstrate that the expression of cAMP-inducible factors involved in steroidogenesis (steroidogenic acute regulatory protein, cytochrome P450 11A1 and 17, and nerve growth factor-induced clone B) and the cAMP-induced biosynthesis of steroid hormones (cortisol and aldosterone) are mediated by PKA and not by EPAC2B. In contrast, both PKA- and EPAC-specific cAMP analogs induced cell rounding, loss of stress fibers, and blocked migration. Taken together, the presented data confirm PKA as the central cAMP mediator in steroid hormone production and reveal the involvement of EPAC2B in cAMP-induced effects on cytoskeleton integrity and cell migration.

scholarly journals Analytical Methods for the Determination of Neuroactive Steroids

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 553
Author(s):  
Michal Kaleta ◽  
Jana Oklestkova ◽  
Ondřej Novák ◽  
Miroslav Strnad
Keyword(s):  
Nervous System ◽  
Steroid Hormone ◽  
Neuroactive Steroids ◽  
Physiological Changes ◽  
Biological Matrices ◽  
Pathological Conditions ◽  
Reliable Monitoring ◽  
Hormonal Steroids ◽  
Endocrine Tissues

Neuroactive steroids are a family of all steroid-based compounds, of both natural and synthetic origin, which can affect the nervous system functions. Their biosynthesis occurs directly in the nervous system (so-called neurosteroids) or in peripheral endocrine tissues (hormonal steroids). Steroid hormone levels may fluctuate due to physiological changes during life and various pathological conditions affecting individuals. A deeper understanding of neuroactive steroids’ production, in addition to reliable monitoring of their levels in various biological matrices, may be useful in the prevention, diagnosis, monitoring, and treatment of some neurodegenerative and psychiatric diseases. The aim of this review is to highlight the most relevant methods currently available for analysis of neuroactive steroids, with an emphasis on immunoanalytical methods and gas, or liquid chromatography combined with mass spectrometry.

Behavioral Endocrinology: Integrating Mind and Body

2020 ◽  
Vol 4 (2) ◽  
pp. 97-110
Author(s):  
Peter T. Ellison
Keyword(s):  
Nervous System ◽  
Steroid Hormones ◽  
Behavioral Ecology ◽  
Endocrine System ◽  
Behavioral Endocrinology ◽  
Paternal Behavior ◽  
Mind And Body ◽  
The Central Nervous System ◽  
Primary Focus

Abstract The nervous system and the endocrine system interact to integrate behavior and physiology. Hormones play an important role in this interaction, particularly steroid hormones. Other molecules, notably oxytocin, can serve both as hormones in the soma and neuromodulators in the central nervous system. Understanding the influence of the endocrine system on human behavior, both individual and social, has been a primary focus of behavioral endocrinology for many decades, though technical and methodological challenges have been formidable. The recent enthusiasm for enzyme-linked immunoassay kits for measuring steroid hormones in saliva has been found to be largely unsound, for example. Despite these difficulties, advances in many areas have been made and new areas, such as the endocrinology of paternal behavior and the role of oxytocin in social interactions, have emerged. Reproductive ecology provides a theoretical framework for integrating the diverse content of human behavioral ecology.

scholarly journals Induction of dopa (3,4-dihydroxyphenylalanine) decarboxylase in blowfly integument by ecdysone. A demonstration of synthesis of the enzyme de novo

1975 ◽  
Vol 146 (1) ◽  
pp. 121-126 ◽  
Author(s):  
E G Fragoulis ◽  
C E Sekeris
Keyword(s):  
Enzyme Activity ◽  
Steroid Hormones ◽  
De Novo ◽  
Steroid Hormone ◽  
Dopa Decarboxylase ◽  
Double Labelling ◽  
Labelling Technique ◽  
Immune Precipitation ◽  
Enzyme Molecules ◽  
Stimulation Of

The activity of the enzyme dopa (3,4-dihydroxyphenylalanine) decarboxylase, present in the epidermis cells of blowfly larvae, increases during the late third instar under the influence of the steroid hormone, ecdysone. By using the double-labelling technique and immune precipitation with univalent antibody to dopa decarboxylase, we demonstrated that the increase in enzyme activity was due to a stimulation of synthesis of enzyme molecules de novo. In this respect, the action of ecdysone is similar to the action of other steroid hormones.

scholarly journals Effects of Chemical Mixtures on the Ovary

Reproduction ◽  
2021 ◽  
Author(s):  
Vasiliki E. Mourikes ◽  
Jodi A Flaws
Keyword(s):  
Ovarian Development ◽  
Steroid Hormone ◽  
Critical Role ◽  
Corpora Lutea ◽  
Chemical Mixtures ◽  
Hormone Production ◽  
Sex Steroid Hormone ◽  
Cellular Processes ◽  
Female Reproductive Health

The ovaries play a critical role in female reproductive health because they are the site of oocyte maturation and sex steroid hormone production. The unique cellular processes that take place within the ovary make it a susceptible target for chemical mixtures. Herein, we review the available data regarding the effects of chemical mixtures on the ovary, focusing on development, folliculogenesis, and steroidogenesis. The chemical mixtures discussed include those to which women are exposed to environmentally, occupationally, and medically. Following a brief introduction to chemical mixture components, we describe the effects of chemical mixtures on ovarian development, folliculogenesis, and steroidogenesis. Further, we discuss the effects of chemical mixtures on corpora lutea and transgenerational outcomes. Identifying the effects of chemical mixtures on the ovaries is paramount to preventing and treating mixture-inducing toxicity of the ovary that has long-term consequences such as infertility and ovarian disease.

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