16 Chapter 1 Testosterone Produced by the Hypothalamus-Pituitary-Gonadal (HPG)-axis (see figure 1.2A), testosterone constitutes an important regulator of social motivational behavior in both males and females, including social approach and avoidance behavior (Hermans & Van Honk, 2006; Mazur & Booth, 1998). Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus, which stimulates the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the pituitary gland. This triggers the production of testosterone and estradiol in the gonads (i.e., testes and ovaries). Testosterone follows a diurnal cycle with the highest levels upon wakening (Diver, Imtiaz, Ahmad, Vora, & Fraser, 2003). Next to the pre- and early postnatal organizational effects on the brain structure, testosterone also affects emotion, motivation and behavior later in life (Lombardo et al., 2012; McHenry, Carrier, Hull, & Kabbaj, 2014). Endogenous testosterone levels can be assessed by blood samples (Serum Testosterone), but also less invasively via (passive drool) saliva samples (Salivary Testosterone). There is intra- variability in testosterone levels, depending on for example, time of the day and menstrual cycle as well as inter-individual variability (e.g., age and sex). Typically, the lower end of the serum concentration range is 4-5 times higher in healthy males compared to the upper end of the healthy female range (Clark et al., 2019; Kanakis, Tsametis, & Goulis, 2019). In addition to testosterone assessment, testosterone can be administrated to individuals (exogenous testosterone) through different methods (i.e., sublingually or using gels or via injections), enabling determination of a causal relationship between testosterone reactivity and its effects on social motivational behavior. Within this dissertation, we applied a single dose (0.5 mg) sublingual testosterone administration. This well-established method has been used in healthy and anxious individuals, showing consistent psychophysiological and behavioral effects approximately 4-6 hours after administration (Bos, Panksepp, Bluthé, & Honk, 2012; Tuiten et al., 2000). Testosterone interacts with other neurotransmitters and -peptides such as oxytocin, vasopressin and dopamine (de Souza Silva, Mattern, Topic, Buddenberg, & Huston, 2009). Moreover, the HPG-axis works in antagonism with the Hypothalamus-Pituitary-Adrenal (HPA)-axis. Specifically, cortisol (end-product of the HPA-axis) has an inhibitory effect on the production and actions of testosterone and vice versa (Toufexis, Rivarola, Lara, & Viau, 2014). Both the HPG and HPA-axis are important in the regulation of social motivational behavior (Mehta & Josephs, 2010; Roelofs, van Peer, et al., 2009b), but within this dissertation I will focus on the HPG-axis and its end product testosterone.
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