1. Structures

The two most important steroid hormones of the adult female are estradiol and progesterone. In addition, estrone and estriol, both weak estrogens, are present in pregnancy. The structures of these compounds are presented in Figures 1 and 2.

Fig1. Estrogens and related molecules. A. The naturally occurring estrogens, of which 17β-estradiol is by far the most active, are shown. B. An estrogen antagonist (clomiphene) and three SERMs (selective estrogen receptor modulators) with mixed agonist/antagonist activities are shown.

Fig2. Progesterone and related compounds. A. Progesterone is the only naturally occurring ligand for the progesterone receptor. B. Many antagonistic ligands for the progesterone receptor have been synthesized of which two are illustrated.

As reviewed in Chapter 2, the naturally occurring estrogens are typically 18-carbon steroids that have an aromatic A ring with a phenolic hydroxyl; the naturally occurring progestin, progesterone, has 21 carbons, with an oxo functionality on both C-3 and C-20. The pathways of synthesis of estradiol and progesterone are covered in Chapter 2 and in section III.B following. The variations in secretion of these hormones during the menstrual cycle are covered in section IV.D.

2. Agonists and Antagonists

 The emergence of a detailed understanding of how steroid hormones interact with receptors to regulate gene transcription led to a new field of research centering on the design of steroid hormone agonists and antagonists, which either mimic or inhibit the natural hormone, respectively. Often the synthesized molecule has turned out to act as an agonist or antagonist in one tissue or group of tissues and have the opposite or no effect in other tissues. In the case of estrogens, these molecules are called selective estrogen receptor modulators, SERMs; the analogous molecules for progesterone are termed selective progesterone receptor molecules, SPRMs.

Shown in Figure 1 are an estrogen antagonist (anti-estrogen), clomiphene, and three SERMs. Clomiphene is a very effective fertility drug for women who fail to ovulate. Because it blocks the feedback inhibition of estrogen on the pituitary and hypothalamus (section IV.C), FSH levels are increased, stimulating the growth of the follicle and increasing the chance of ovulation. Tamoxifen acts as an antagonist in breast tissue (and an agonist in the uterine endometrium) and is used in the treatment of hormone-receptor positive breast cancer. Raloxifene behaves as an agonist in bone tissue (and an antagonist in the uterus and breast) and is used to ameliorate the bone loss that occurs and leads to osteoporosis in postmenopausal women. Bazedoxifene is a newer SERM, similar in its actions and use (in the EU and Japan) to raloxifene.

Figure 2 shows the structures of two progesterone antagonists. Because progesterone from the corpus luteum is absolutely essential for the maintenance of pregnancy in its early weeks, the antagonistic activity of RU-486 has been used for inducing abortions shortly after conception. Both RU-486 and ulipristal acetate are under investigation for their ability to reduce uterine fibroids in women during their reproductive years, thus obviating the need for surgery for this condition.

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

The Androgen Receptor

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