8β-VE2, or 8β-vinylestradiol, also known as 8β-vinylestra-1,3,5(10)-triene-3β,17β-diol, is a synthetic

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...

featuring an

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

core. It is a highly potent and selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

ERβ Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...

that is used in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific ...

to study the function of the ERβ. It has 190-fold higher potency in

transactivation In the context of gene regulation: transactivation is the increased rate of gene expression triggered either by biological processes or by artificial means, through the expression of an intermediate transactivator protein. In the context of recep ...

assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of ...

s of the ERβ relative to the

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex h ...

and 93- (rat) and 180-fold (human) preference in

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mo ...

for the ERβ over the ERα. In rodents, 8β-VE2 stimulates follicular growth and to a comparable extent as estradiol, whereas the highly ERα-selective agonist

16α-LE2 16α-LE2, or 16α-lactone-estradiol, also known as 3,17β-dihydroxy-19-nor-17α-pregna-1,3,5-(10)-triene-21,16α-lactone, is a synthetic, steroidal estrogen featuring an estradiol core. It is a highly potent and selective agonist of the ERα that ...

has no effect on

ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with t ...

development, indicating that the ERβ and not the ERα is involved in the effects of estrogen on ovarian follicles. In contrast, 16α-LE2 stimulates

uterine The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uteru ...

weight, whereas 8β-VE2 has no effect, indicating that the ERα and not the ERβ is involved in the effects of estrogen on the uterus. Research has determined through experimental rodent studies with estradiol, 16α-LE2, and 8β-VE2 that the positive, protective effects of estrogens on

bone formation Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by Cell (biology), cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes ...

resorption and

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...

are mediated via the ERα, whereas the ERβ does not appear to be involved. On the other hand, while both ERα and ERβ are expressed in

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...

, it was found that ERβ is the predominant ER subtype that is responsible for estrogen stimulation of skeletal muscle growth and regeneration. Moreover, similarly to

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteris ...

, 8β-VE2 has

anabolic Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-d ...

effects in skeletal muscle and significantly increases muscle mass as well as produces

muscle hypertrophy Muscle hypertrophy or muscle building involves a hypertrophy or increase in size of skeletal muscle through a growth in size of its component cells. Two factors contribute to hypertrophy: sarcoplasmic hypertrophy, which focuses more on increased ...

in rats. In contrast to testosterone however, 8β-VE2 shows no androgenic effects. The effects of 8β-VE2 and ERβ may be mediated, in part, by local stimulation of

insulin-like growth factor 1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans i ...

(IGF-1)-induced

myogenic The myogenic mechanism is how arteries and arterioles react to an increase or decrease of blood pressure to keep the blood flow constant within the blood vessel. Myogenic response refers to a contraction initiated by the myocyte itself instead ...

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...

, as 8β-VE2 has been found to strongly induce expression of IGF-1 in the rat

levator ani The levator ani is a broad, thin muscle group, situated on either side of the pelvis. It is formed from three muscle components: the pubococcygeus, the iliococcygeus, and the puborectalis. It is attached to the inner surface of each side of th ...

muscle.

References

{{Estrogen receptor modulators Estranes Selective ERβ agonists Synthetic estrogens Vinyl compounds

See also

References