Inhibin, beta B, also known as INHBB, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''INHBB''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
INHBB is a subunit of both
activin and inhibin
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual c ...
, two closely related glycoproteins with opposing biological effects.
Function
Inhibin
Inhibins are heterodimeric
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
s composed of an α subunit (
INHA) and one of two homologous, but distinct, β subunits (
βA or βB, this protein). mRNA for the two subunits has been demonstrated in the
testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
of adult rats.
Inhibin can bind specifically to testicular interstitial cells throughout development and may be an important regulator of
Leydig cell
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
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 system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
production or interstitial cell function.
The inhibin beta B subunit joins the α subunit to form a pituitary
FSH secretion inhibitor. Inhibin has been shown to regulate gonadal stromal cell proliferation negatively and to have tumour-suppressor activity. In addition, serum levels of inhibin have been shown to reflect the size of granulosa-cell tumors and can therefore be used as a marker for primary as well as recurrent disease. Because expression in gonadal and various extragonadal tissues may vary severalfold in a tissue-specific fashion, it is proposed that inhibin may be both a growth/differentiation factor and a hormone.
Activin
Furthermore, the beta B subunit forms a homodimer, activin B, and also joins with the beta A subunit to form a heterodimer, activin AB, both of which stimulate FSH secretion.
Tissue distribution
Sections of testicular tissue from rat revealed positive immunoreactivity against anti-inhibin intensely appeared in
Leydig cell
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s.
In adult animals, binding of
125I inhibin was localized primarily to the interstitial compartment of the testis.
Also, Jin et al., (2001) reported that Leydig cells showed strong positive staining for the inhibin βA subunit in pigs testis.
Receptors
In situ ligand binding studies have shown that
125I inhibin βA binds specifically to Leydig cells throughout rat testis development. These results suggest that inhibin has been considered as a regulator of Leydig cell differentiated function.
Recently, additional inhibin specific binding proteins were identified in inhibin target tissues, including pituitary and Leydig cells.
From these receptors betaglycan (the
TGF-β type III receptor) and
InhBP/p120 (a membrane-tethered
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
) were identified as putative inhibin receptors and they are all present in Leydig cells. However, a faint positive reaction was detected in Leydig cell
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
in rats treated with
anise
Anise (; '), also called aniseed or rarely anix is a flowering plant in the family Apiaceae native to Eurasia.
The flavor and aroma of its seeds have similarities with some other spices and herbs, such as star anise, fennel, licorice, and ta ...
oil.
This may be related to the damaged Leydig cells, as a result of the decreasing of inhibin expression. This may be related to its content of
safrole
Safrole is an organic compound with the formula CH2O2C6H3CH2CH=CH2. It is a colorless oily liquid, although impure samples can appear yellow. A member of the phenylpropanoid family of natural products, it is found in sassafras plants, among oth ...
.
Cancer
INHBB gene has been observed progressively downregulated in
Human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
-positive
neoplastic keratinocytes derived from uterine cervical
preneoplastic lesions at different levels of malignancy.
For this reason, INHBB is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical
preneoplastic lesions progression.
References
Further reading
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{{NLM content
Estrogen regulation