**6. References**

134 Steroids – Basic Science

factors (social, psychological or biological) contribute to modulating human sexual behavior. Because gender-appropriate rearing, and not the chromosomal, gonadal or genital factors plays a crucial role in gender identity development, early diagnosis and treatment if patients

Sex assignment of children with DSD is a subject of intense debate. The early pioneers in this field coined the term 'optimal gender policy', which advocated for early corrective surgery to help the affected children and their parents to facilitate stable gender identity and appropriate gender role behavior (Money et al., 1955) . Opponents of early surgery argue for a 'full consent policy', in which surgery is not performed in non-emergency situations before full consent may be obtained from the child (Kipnis § Diamond, 1998). In 17-HSD3 deficiency, as in all situations characterized by severe undervirilization (Sinnecker stage 5 or 4), is not always feasible to wait the start of the virilization and/or the age for a reliable full consent for major intervention, because in this waiting period the patient could assume a female gender role and identity. According to the recent guidelines regarding ethical principles and recommendations for the medical management of DSD in children and adolescents, the parents take the first-line responsibility in defining what might be best for the child, and this might vary according to their individual experience and lifestyle, cultural expectations and religious beliefs (Wiesemann et al., 2010). The child, according to his or her developmental level, can express own preference. Each case must be weighed on its own merits. When there is a doubt, the psychological and social support of the child and the

The external genitalia are mostly female in 17-HSD3 deficiency, but the internal structures are derivatives of wolffian structures. The testes are usually positioned in the inguinal canal, sometimes at the labia majora and rarely in the abdominal cavity (Mendonca et al., 2000). The consensus statement for management of DSD puts the risk of germ cell malignancy at 28% in 17-HSD3 deficiency (Houk et al., 2006; Hughes et al., 2006). This puts it in the intermediate risk group for malignancies and close monitoring is recommended for someone who is raised as a male rather than having gonadectomy at the time of diagnosis.

Diagnosis and consequently early treatment of the 17-HSD3 deficiency is frequently difficult because clinical signs are often mild or absent from birth until puberty. Moreover, the 17-HSD3 deficiency is clinically indistinguishable from other forms of 46,XY DSD such as AIS or 5-reductase 2 gene deficiency. The correct diagnosis can be arrived at by systematic endocrine evaluation and, most importantly, by the calculation of the T/4-A ratio. The diagnostic power of biochemical parameters is not always specific, because no normal reference range has yet been established in strictly age-matched controls and because of overlapping with other causes of 46,XY DSD due to impaired T biosynthesis. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. A high index of suspicion should be present for any female who presents with inguinal hernias or mild clitoromegaly in infancy or early childhood. The virilization in the

parent is to be ranked higher than the creation of biological normalcy.

with the 17-HSD3 deficiency is very important.

**4.9 Psychological aspects** 

**4.10 Malignancy risk**

**5. Conclusions** 


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**8** 

*Australia* 

**Steroid Hormones in** *Drosophila***:** 

Naomi Mitchell1 and Ross Hannan2,3,4

**How Ecdysone Coordinates Developmental** 

**Signalling with Cell Growth and Division** 

Leonie Quinn1, Jane Lin2, Nicola Cranna1, Jue Er Amanda Lee1,

*3Department of Biochemistry and Molecular Biology, University of Melbourne,* 

Ecdysone is the major steroid hormone in all holometabolous insects responsible for driving the metamorphosis of larval tissues into adult structures. During metamorphosis, ecdysone is essential for upregulating the genes required to control apoptosis and differentiation, essential processes for removal of larval structures which have become obsolete and for tissue remodelling. In addition, ecdysone directs cell growth and division in many tissues throughout the larval to pupal transition. This chapter will discuss the many diverse mechanisms reported for connecting the ecdysone pulse to the developmentally regulated cell growth and cycle progression required for tissue growth and for insects to reach their

Like all other holometabolous insects, the size of *Drosophila* adult flies is set by the size of the larvae prior to metamorphosis, at the time of pupariation when feeding has ceased and growth can no longer occur. The major developmental hormone in *Drosophila*, the steroid hormone 20-hydroxyecdysone (20E), commonly known as ecdysone, is required for all the developmental transitions needed for metamorphosis (Figure 1-3; (Thummel 1995, 1996, 2001)). Ecdysone is produced in and released by the prothoracic gland (PG), a component of the ring gland, which also contains the corpora allata (CA) and corpora cardiaca (CC) (Figure 1; (Zitnan et al. 2007; McBrayer et al. 2007)). Ecdysone release is controlled by a complex combination of upstream factors, including peptide hormones and neuropeptide signals (see section 2.2). For example, Prothoracicotropic hormone (PTTH) from the central nervous system (CNS) is required to regulate the synthesis and release of ecdysone from the

Ecdysone pulses from the PG are required for all aspects of morphogenesis, starting with the formation of the body plan during late embryogenesis, hatching and development of the first larval instar, and for cuticle moulting at the end of the first and second instars. A large

**1. Introduction** 

target body size.

PG (McBrayer et al. 2007).

**1.1 The ecdysone pathway directs** *Drosophila* **development** 

*1Department of Anatomy and Cell Biology, University of Melbourne, 2Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne,* 

*4Department of Biochemistry and Cell Biology, Monash University,* 

