1. Testosterone

There are three possible levels at which testosterone can exert negative feedback on gonadotrophin secretion: the kisspeptin neurons of the arcuate nucleus which regulate the output of GnRH neurons; the GnRH neurons, themselves; and the pituitary gonadotrophs. The relative contribution of each of these com ponents to overall LH and FSH secretion varies with species, but each probably contributes to the negative feedback effect of testosterone in humans.

Kisspeptin neurons contain both androgen and estrogen receptors and testosterone represses KiSS1 gene expression in these neurons in the arcuate nucleus. This leads to decreased GnRH secretion by the hypothalamic neurons that receive kisspeptin signals. Studies in humans in whom aromatase activity is blocked suggest that both testosterone and estradiol suppress kisspeptin expression and activity and that testosterone does not require aromatization for this activity. The relative contribution of the negative feedback effect of testosterone at the kisspeptin neuron and directly at the GnRH neuron in the human is not yet settled, although it is clear that the former is a major component of this action of testosterone.

In the pituitary, testosterone decreases the transcription of the β-subunits of LH and FSH. In contrast to the situation in kisspeptin neurons, in pituitary gonadotrophs, aromatization of testosterone to estrogen plays an important role in the feedback effects of testosterone.

2. Inhibins and Activins

The secretion of both LH and FSH from gonadotrophs is stimulated by the same releasing hormone, GnRH. At the same time it is clear from physiological observations that the two gonadotrophins are differentially regulated. For example, in experimental animals in which the testes are removed, FSH levels rise and are not suppressed by administration of testosterone or estradiol. There are several mechanisms that contribute to this differential regulation. One is that FSH and LH respond differentially to the pulses of GnRH which differ in amplitude and frequency. Additionally, the gonads produce, in response to stimulation by FSH, the peptide hormone inhibin which preferentially inhibits FSH secretion from gonadotrophs. In the testis, inhibin is produced and secreted by the Sertoli cells.

As depicted in Figure 1 the two heterodimeric isoforms of inhibins share a common 18 kDa α subunit and have one of two closely related 14 kDa β subunits. The α and β subunits are joined by disulfide bonds. The two forms are referred to as inhibin A (αβA) or inhibin B (αβB). Along with the activins, the inhibins belong structurally to the transforming growth factor (TGFβ) multigene family, which also includes the bone morphogenetic proteins (BMPs), and anti-Müllerian hormone (AMH).

Fig1. The inhibin/activin peptides. The inhibins and activins are a group of peptides that are part of the transforming growth factor β superfamily of pleiotropic growth factors. They consist of two subunits joined by a disulfide bond. Inhibins consist of one 18kDa α subunit and one of the two closely related 14kDa β subunits, A and B. Activins are composed of two β subunits. Each dimeric activin or inhibin is named according to the β subunit(s) it contains.

Activins are either heterodimers or homodimers of the two β subunits of inhibin, e.g., either βAβB, βAβB, or βBβB (see Figure 12-10). Locally produced activins stimulate FSH release from the pituitary, an action which can be blocked by inhibin. Activins play other roles in reproduction in males and females and are also important in such cellular processes as differentiation, proliferation, migration, adhesion, and apoptosis.

Activins stimulate the tonic secretion of FSH by the pituitary. Inhibin (specifically Inhibin B in rodents and humans) binds to the activin type II receptor with low affinity, but this affinity is increased when the coreceptor, TGFβ receptor 3 (TGFBR3), also known as betaglycan, is present. This binding blocks activin binding to its receptor, thereby decreasing FSH secretion. In addition to their role in the regulation of FSH secretion, inhibins are important in other aspects of reproduction, for example in testis development and spermatogenesis.

اخر الاخبار

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

تفوق على البشر.. روبوت يحطم الرقم القياسي لسباق نصف ماراثون !

المزيد

مواضيع ذات صلة

Control of the Ovary by the Hypothalamus and Pituitary

Synthesis of Progesterone and Estrogens

Female Steroid Hormones

The Androgen Receptor

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