The primary structure of the hypothalamic decapeptide gonadotropin-releasing hormone (GnRH; Figure 1) appears to be identical in all mammals, with the exception of the guinea pig, and there is a high degree of conservation of the sequence across the vertebrates. The GnRH precursor protein is also highly conserved across species, consisting of (from the amino to the carboxyl terminus) a 23 amino acid signal peptide, GnRH, a proteolytic cleavage site (GKR), and the 56 amino acid GnRH associated peptide (GAP). GAP is co-secreted with GnRH following processing of the precursor into the mature peptides in the secretory granules of the GnRH neurons. Other forms of GnRH have been identified in which amino acid variations occur at positions 5, 7, and/or 8 and which differ in species and tissue distribution.

Fig1. Hypothalamic peptides that control anterior pituitary hormone secretion. The amino acid sequences of some important hypothalamic regulatory peptides are indicated schematically, reading left to right, N- terminal to C-terminal. TRH and GnRH, the smallest of the peptides, have modifications on both ends, with a pyroglutamyl moiety (red hexagon) and amidation of the C-terminal carboxyl group (yellow diamond). CRH and GHRH have only the N-terminal modification, whereas somatostatin is not modified at either end. The sequence of somatostatin-28 is shown with both lightly and darkly shaded circles. The darker carboxyl terminal 14 amino acids are those of somatostatin-14.

GnRH is absolutely required for reproductive function. In its absence, secretion of the two gonadotrophic hormones that depend on it is either completely (luteinizing hormone, LH) or greatly (follicle stimulating hormone, FSH) diminished.

The secretion of GnRH from the neurons in which it is synthesized is characterized by its pulsatile nature, as shown in Figure 2. In most mammals, including humans, it is difficult to measure GnRH directly due to the small amount secreted and its short half-life. Therefore the measurement of the electrophysio logical activity of a group of GnRH neurons has been accepted as a surrogate for the measurement of the actual hormone. In this way, the pulses of LH secretion from the pituitary can be correlated as occurring with or shortly following secretion of GnRH from its neurons, as shown by the classical example of such a study shown in Figure 2. Other studies show that when the pulsatility of GnRH secretion is interfered with experimentally both LH and FSH secretion are severely affected. Furthermore, the two gonadotropins show pulse frequency discrimination, with LH responding to faster frequencies of the GnRH pulse and FSH to slower frequencies.

Fig2. Demonstration of the pulsatility of GnRH and LH secretion in the monkey. In the lower part of the figure is shown the pulsatile nature of the firing of GnRH secreting neurons given as Multiple Unit Activity (MUAs). Above are the measured plasma levels of LH in the same animal over the same time course. Adapted from Cardenas et al., Proc. Nat. Acad. Sci. 90:9360 (1993).

The pulse generator for GnRH secretion is now thought to lie in neurons of the pre-optic area that contain a triad of neuropeptides, kisspeptin, neurokinin B, and dynorphin (the so-called KNDy neurons), which project into the cell bodies and terminals of GnRH neurons of the hypothalamus. Inactivating mutations in kisspeptin lead to some types of hypogonadism and infertility in humans and this peptide will be the subject of further discussion in Chapters 12 and 13.

The human GnRH receptor, like the TRH receptor and other GPCRs, has a seven-membrane-spanning domain and the extracellular domains are qualitatively similar; the intracellular domains are distinct in that the cytoplasmic tail is absent from the GnRH receptor. The primary signaling pathway for gonadotropin secretion is through activation of phospholipase C, release of IP3 and DAG (diacylglycerol), and activation of protein kinase C. These signals are transmitted to the nucleus through the JNK (c-junN-terminal kinase) pathway to activate transcription of the gene for the β-subunit of either LH or FSH. In addition, elevated cyclic AMP and intracellular Ca2+ from activation of voltage-sensitive calcium channels both contribute to stimulus of secretion of stored GnRH.

اخر الاخبار

اخبار العتبة العباسية المقدسة

دار الكفيل تنهي طباعة كتاب (لمَ لا) تمهيدًا لمناقشته في ملتقى غيث السماء القرآني الثاني

العتبة العباسية المقدسة تطلق مسابقتها الثقافية بذكرى ولادة الإمام زين العابدين (عليه السلام)

العتبة العباسية المقدسة تكرّم 1000 طالبة من المرتديات العباءة العراقية في مدارس الديوانية

العتبة العباسية المقدسة تؤكد أهمية الحجاب كجزء من منظومة الواجبات الشرعية

المزيد

الآخبار الصحية

الخبز الأسمر أم الأبيض.. أيهما أفضل لضبط سكر الدم؟

عقاقير التخسيس و"الانتحار".. الحكومة الأميركية تحسم الجدل

الهرم الغذائي الجديد.. لماذا يعد "انقلابا" في خارطة الطعام؟

لحماية ظهرك وقلبك في آن واحد.. ما وضعية النوم الصحيحة؟

المزيد

الآخبار التكنلوجية

كيف يعزز الضوء الطبيعي تفكيرك وانتباهك خلال اليوم

سابقة.. طاقم من محطة الفضاء الدولية يعود إلى الأرض مبكرا

منصات التواصل تضرّ بنفسية المراهقين… والفتيات الأكثر تأثرا

ابتكار ألماني قد يغيّر مستقبل صناعة البلاستيك

المزيد

مواضيع ذات صلة

Thyrotropin-Releasing Hormone

Biosynthesis of Adrenal Cortex Mineralocorticoids, Glucocorticoids, and Some Androgens

Mechanisms of hormone action: Cell Signaling by Membrane Receptors

Biosynthesis of Peptide and Protein Hormones

Hormones and Their Communication Systems

Stepwise development of tissue- specific insulin resistance

Insulin resistance in adipose tissue Adipose tissue

Insulin resistance in the liver

Insulin resistance in skeletal muscle

Insulin resistance as a risk factor for type 2 diabetes

Definition and measurement of insulin resistance in humans

Hypoglycemia without Diabetes