Table 1 summarizes many of the biological actions of testosterone or one of its biologically active derivatives, 5α-dihydrotestosterone or estradiol (see Figure 1) in target tissues. The biological effects of the androgenic steroids, testosterone or DHT, in the male reproductive system as well as in those tis sues associated with the secondary sex characteristics are all believed to be due to the association of the hormone with the androgen receptor, AR. The human AR gene lies on the X chromosome and encodes a protein of 919 amino acids. AR is ubiquitously expressed although its levels and therefore androgen sensitivity varies substantially among nonreproductive tissues.

Table1. Biological Responses to Testosterone and Its Derivatives

Fig1. Testosterone action pathways. In many target tissues of androgens, typified by the skeletal muscle, testosterone (T) is the molecule that interacts with the androgen receptor (AR) to generate biological responses. In other tissues, of which the hair follicles of the skin and the prostate gland are examples, testosterone undergoes 5α-reduction to form 5α-dihydrotestosterone (DHT), which interacts with the AR with greater affinity than does T; 5–10% of T secreted by the testis undergoes this transformation in target tissues. Finally, a small, but important, amount of T is aromatized in target tissues to form estradiol (E2) which interacts with the estrogen receptor (ER). Cells in the bone and the brain provide examples of this pathway.

The AR has a structure typical of its class of nuclear receptors (see Chapter 1) with an N-terminal transactivating domain; a middle DNA-binding domain with two zinc fingers; and, following a short hinge region, a C-terminal ligand binding domain. There are some homopolymeric repeat sequences that show consider able polymorphism. Among these are the highly variable polyglutamine tract and the less variable glycine variant. The occupied AR acts as a transcription fac tor that either increases or decreases the expression of specific genes in target tissues to bring about biological responses or phenotypic changes. The length of the polyglutamine tract, which varies between 5 and 35 residues in human populations, is inversely related to the transcriptional efficiency of the AR.

The AR is among the nuclear receptors that, in the absence of ligand, are located in the nucleus or cytoplasm as complexes with chaperone proteins. Upon ligand binding the AR changes conformation, the chaperone proteins dissociate, and the liganded receptor is available to bind to specific androgen receptor elements on the DNA.

Several hundred mutations of the AR have been identified and these lead to various degrees of androgen insensitivity. Some are in the ligand binding domain, affecting the ability of the AR to maintain a stable complex with its ligand; others are in the DNA binding domain, so that even when ligand is bound, the hormone receptor complex is unable to carry out its function of binding to DNA. Collectively these defects lead to clinical disorders categorized as the androgen insensitivity syndrome (AIS), which is the most common of the hormone insensitivity conditions and is discussed in section VI.B following.

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اخبار العتبة العباسية المقدسة

شعبة التوجيه الديني النسوي تنظم مسابقة ثقافية بذكرى ولادة السيدة المعصومة (عليها السلام)

المجمع العلمي ينظّم محاضرةً تربوية لطلبة مشروع حفظ القرآن الكريم في كربلاء

قسم الشؤون الفكرية يقيم معرضًا وثائقيًا ضمن مهرجان (الشهيد) في جامعة الكوفة

قسم الشؤون الدينية يشهد إقبالًا واسعًا من المؤمنين لتنظيم عقود الزواج

المزيد

الآخبار الصحية

دواء جديد يحمي القلب ويعزز علاج السرطان في آن واحد

سر غذائي بسيط لحماية القلب مع التقدم في العمر

علامات تشير إلى اختلال عمل الغدة الدرقية

السمنة واللقاحات.. دراسة تكشف تأثيراً سلبياً

المزيد

الآخبار التكنلوجية

البعوض في آيسلندا إشارة مبكرة على تحولات بيئية في القطب الشمالي

صاروخ يطلق قمرا اصطناعيا في مدار خاطئ

"أوبن إيه آي" تطلق نموذجا للعلوم الحيوية واكتشاف الأدوية

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المزيد

مواضيع ذات صلة

Control of the Ovary by the Hypothalamus and Pituitary

Synthesis of Progesterone and Estrogens

Female Steroid Hormones

Hypothalamic-Pituitary-Testis Axis: Feedback Control

Causes of Destructive (Low RAIU) Thyrotoxicosis

Causes of Hyperthyroidism

Hypothalamic-Pituitary-Testes Axis: Hormonal Control of the Testis

Sex Hormone-binding Globulin

Modification of Testosterone in Target Tissues

Clinical Aspects of Hormones of the Adrenal Medulla: Chronic Stress

Biological Responses to Epinephrine

Adrenergic Receptors