Are there testosterone receptors in female mammary tissue?

Are there testosterone receptors in female mammary tissue?

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Does female mammary tissue have receptors for testosterone hormones?

Do male hormones influence female mammary glands, as female hormones influenced the male mammary tissue, such as in gynecomastia?

The female mammary gland tissue contains androgen receptors (testosterone is an androgen). So this tissue is sensitive to androgens, and they inhibit the estrogen-induced proliferation. The inactivation of the androgen receptor on the other hand leads to an accelerated growth of the pubertal mammary gland and to the upregulation of estrogen receptor α expression in female mice. See references 1-3.

And the androgen receptor also seem very important in the formation of the nipples, as testosterone here directs apoptosis in the forming breast tissue. Mice without a functioning androgen receptor were born without nipples. See reference 4 and 5 for details.

To answer your question shortly: Yes, androgen hormones (among them testosterone) have a profound influence on the female mammary gland.


  1. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression.
  2. Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene
  3. Androgen receptor inactivation resulted in acceleration in pubertal mammary gland growth, upregulation of ERα expression, and Wnt/β-catenin signaling in female mice.
  4. Hormone Action in the Mammary Gland
  5. Specificity of tissue interaction and origin of mesenchymal cells in the androgen response of the embryonic mammary gland.

Testosterone therapy and breast histopathological features in transgender individuals

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months p < 0.01 adjusted p = 0.01), fibroadenoma (median = 14.8 months p = 0.02 adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months p < 0.001 adjusted p < 0.001), and papillomas (median = 14.7 months p = 0.04 adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

Hyperplastic changes and receptor status in the breast tissue of bodybuilders under anabolic-androgenic steroid stimulation

Anabolic androgenic steroids (AAS) are misused by athletes to improve their physical performance. AAS with similar groups and configuration indicate that testosterone is the base of this ability to stimulate anabolic activity. The effect of these compounds on the breast tissue of males that consume them is a confirmation of its metabolic pathway. To confirm its hormonal effects, the status of estradiol and progesterone receptors (ER, PgR) status was determined in cytoplasmic and nuclear fractions (HRc, HRn) of 8 premalignant breast tissues from 8 bodybuilders (aged 21 to 45 years) under AAS stimulation. The control group included 5 males with benign disorders of the breast, but not due to AAS administration. The concentrations of ERc and ERn were significantly higher (p < .05) in males under AAS stimulation than in males without these. The concentrations of PgRc and PgRn do not differ between these two groups (p > .05) The benign breast disease is remarkably similar in female and male patients, suggesting a common origin. In the same way, the measurement of both HRc and HRn is necessary to accurately report receptor concentration.


Effects of sex steroids and tamoxifen on mammary epithelial proliferation

The mammary epithelial proliferation index (MEPI) was determined by immunodetection of the Ki-67 antigen, which is a nonhistone, nuclear matrix protein specific for proliferating cells (16). Mammary epithelial Ki-67 immunoreactivity is exclusively nuclear and is concentrated in 2–3 focal nuclear deposits (Fig. 1). The MEPI is quite low in ovariectomized, placebo-treated monkeys and is increased sixfold by E2 treatment (Fig. Combined P4 and E2 treatment produced the same degree of epithelial proliferation as E2 alone, but the addition of testosterone (T) to E2 treatment attenuated E2's proliferative effects by

40% (P<0.002). Hormone levels in the different treatment groups are shown in Table 1. It is noteworthy that the MEPI is significantly reduced in E2/T-treated animals, even though E2 levels were higher in this group compared with the E2 and E2/P4 groups. Tamoxifen treatment of ovariectomized monkeys produced an approximate threefold increase in proliferation compared with placebo (Fig. 1). The effects of tamoxifen and E2/T on MEPI were not statistically different (P=0.15).

Mammary epithelial proliferation shown by Ki-67 immunoreactivity in ovariectomized monkeys treated with vehicle (A), estradiol (B), E2 and progesterone (C), tamoxifen (D), and E2 plus testosterone (E). Representative mammary gland sections are shown in panels A–E, and quantitation of the mean percentage of Ki-67 positive nuclei in each treatment group is shown in panel F. Data represent means plus se for 4–6 animals per group. An asterisk connotes P < 0.01 with respect to the placebo group. Bar = 100 μ.

Androgen and estrogen receptors

To determine whether testosterone's inhibitory effects on the MEPI could be androgen receptor mediated, androgen receptor expression was examined using in situ hybridization (Fig. 2). AR mRNA is concentrated in mammary epithelium but is also detected in scattered stromal cells (Fig. 2A). AR mRNA levels are equal in ovariectomized and E2-treated animals, but are significantly reduced by E2/T and by tamoxifen (Fig. 3A). Estrogen receptor (ERa) mRNA is uniformly distributed in the mammary epithelium and is abundant in the wall of mammary arteries (Fig. 2B, C). ERα mRNA is increased by

50% in the E2-treatment group combined E2/P4 treatment has a lesser but still significant positive effect on ERα expression (Fig. 3B). Addition of testosterone to E2 treatment, however, completely inhibited E2's positive effect on ERα expression. Tamoxifen treatment resulted in reduction of ER mRNA levels below control (placebotreated ovariectomized monkeys) values (Fig. 3B). ERβ mRNA was not detected in the primate mammary epithelium. Noting that combined E/T and tamoxifen treatments had parallel effects on estrogen and androgen receptor expression pattern, we investigated ApoD gene expression in the mammary gland, since this factor is known to be androgen regulated in mammary cells (17). ApoD mRNA is significantly reduced by both E2/T and by tamoxifen treatments (Fig. 4A). In another study examining insulin-like growth factor binding protein (IGFBPs 1– 6) gene expression in these mammary glands, we found that there were no significant sex steroid effects on IGFBP mRNA levels (18) except for IG-FBP5. IGFBP5 mRNA is not affected by E2 alone but is increased by E2/T and tamoxifen (Fig. 4B).

AR (A) and ERα (B, C) mRNA localization in primate mammary gland. The hybridization signal appears as red grains. The signal for both receptors is concentrated over alveolar epithelial cells. ERα mRNA is also abundant in the intima media of mammary arteries (C). Nonspecific signal generated by sense probe hybridization is seen in panel D. Bar = 250 μ.

Effect of sex steroids and tamoxifen on androgen (A) and estrogen (B) receptor mRNA levels in primate mammary epithelium. mRNA values are in grains per 400 μm 2 . Data are the means + se for 4–8 animals per group. a, P< 0.03 b, P< 0. 006c, P < 0.0001 d, P< 0.0004 compared to the relevant control group.

Effect of sex steroids and tamoxifen on apolipopro-tein D (A) and IGFBP5 (B) mRNA levels in primate mammary epithelium. mRNA values are in grains per 400 μm 2 . Data are the means + se for 4–8 animals per group. a, P < 0.005 b, P < 0.002 c, P < 0.001 d, P < 0.05 compared to the relevant control group.

E2 (pg/ml) P4 (ng/ml) T (ng/dl)
Control 6.30 ± 0.55 0.17 ± 0.03 36.73 ± 7.17
E2 400.23 ± 120.74 0.23 ± 0.01 49.55 ± 1.05
E2/P4 355.60 ± 18.45 3.37 ± 0.33 19.81 ± 3.38
E2/T 1149.67 ± 264.89 2.36 ± 1.07 130.33 ± 9.74
Tamoxifen 7.81 ± 1.39 0.32 ± 0.07 nd
  • a Serum hormones were measured by RIA 3 days after pellet implantation, when mammary tissue was collected for analysis. Data are means ± se for 4–8 animals in each group. E2 levels are higher in the E2/T group because these animals received an E2 dose of 1 mg/kg, whereas the other E2 groups received a standard 5 mg dose.

Transcription factor and protein interactions

AR and FOXA1

Prostate cancer

FOXA1 is a transcription factor which plays an important role in aiding the binding of hormone receptors to their target DNA 16 . More recently, three distinct classes of alterations in FOXA1 have been described in prostate cancer, each with unique structural and phenotypic consequences 17 . The Class-1 activating mutations originate in early prostate cancer without alterations in ETS or SPOP and are found in the wing-2 region of the DNA-binding forkhead domain. Functionally these mutations allow for enhanced chromatin mobility and binding frequency and strongly transactivate a luminal AR program. The second class of activating mutations are found in metastatic prostate cancer and are characterized by a truncated C-terminal domain. These mutations increase FOXA1 DNA affinity and promote metastasis by activating the Wnt pathway through TLE3 inactivation. The final class of FOXA1 genomic rearrangements are characterized by duplications and translocations within the FOXA1 locus that reconfigure regulatory elements (FOXA1 mastermind elements) to drive overexpression of FOXA1. This third class of alterations is found primarily in metastatic prostate cancer and further underscores the interaction and significance of AR and FOXA1 protein interactions 17 . Similar classes of alterations also been observed in breast cancer 1 . In prostate cancer, FOXA1 also influences the ability of AR to bind DNA and control cell cycle progression. FOXA1 binds to genes necessary for growth of castration-resistant prostate cancer (CRPC), suggesting that FOXA1 is responsible for driving cell cycle progression in CRPC both from G1 to S and G2 to M 18 . FOXA1 also facilitates cell cycle progression from G2 to M by acting as a cofactor for AR 18 . Unsurprisingly, there is also significant overlap between genomic binding sites occupied by AR and FOXA1 19 . While AR binds to many DNA regions independent of FOXA1, DNA-binding sites often require the presence of FOXA1 for AR recruitment 19 . Therefore, loss of FOXA1 results in the inability of AR to bind many DNA loci 19 . Using H3K4me2 ChIP analyses, Sahu et al. found that there were H3K4me2 marks at

70% of sites shared by AR and FOXA1 19 . Furthermore, staining of FOXA1 has been shown to correlate with disease outcomes in prostate cancer patients, where even with high AR staining, low FOXA1 is associated with good prognoses, and strong FOXA1 staining correlates with poor prognoses 19 , indicating that FOXA1 may have an important effect on AR signaling and tumor progression. Levels of FOXA1 are also elevated in prostate tumors and metastases, and overexpression of FOXA1 in prostate cancer cell lines results in increased AR binding at novel sites that have high chromatin accessibility 20 . These results suggest that increased levels of FOXA1 enhance AR binding to novel sites in order to facilitate cancer cell growth 20 and implicate the importance of FOXA1 on AR function and tumor progression.

Breast cancer

FOXA1 is also essential for the growth of ER+ breast cancer cell lines 21 . Similar to prostate cancer, ChIP-seq studies have shown that there is extensive overlap between locations of AR and FOXA1 binding in breast cancer cells 22 . The function of AR in breast cancer is also dependent upon FOXA1, as silencing of FOXA1 inhibits AR binding of target DNA as well as cell growth 22 . In addition, FOXA1 functions as a transcription factor, playing an important role in aiding binding of hormone receptors, including ER and AR, to their target DNA 16,23 . When expressed with AR, FOXA1 may direct AR binding at sites of ER binding in luminal tumors 24 . Notably, co-expression of AR and FOXA1 was observed by immunohistochemistry (IHC) in

15% of triple-negative breast cancer (TNBC) patients 24 , and AR-positive (AR+), FOXA1-positive (FOXA1+) patients had a significant decrease in recurrence-free survival and overall survival compared to TNBC patients 25 . These findings suggest that when co-expressed in TNBC, AR, and FOXA1 may be mediating an estrogen-like gene signature similar to those expressed in luminal breast cancers. FOXA1 has been studied extensively in the context of ER chromatin binding, and ER binding is dependent on FOXA1 in the presence or absence of ligand 23 . Further, similar to findings in prostate cancer, 1.8% of breast cancers harbor mutations in FOXA1, and amplifications of the FOXA1 gene locus have been observed in breast and prostate cancers 26 . Notably most identified mutations are in the forkhead domain of FOXA1, and tumors in this study were exclusively ER+. The implications of these mutations, however, is still under investigation in breast cancer. Interestingly, differences exist between the function of FOXA1 in directing AR binding in breast versus prostate cancers, and future studies may investigate the varied roles of FOXA1 in directing AR binding in TNBC and prostate cancer, in addition to investigating the role of AR when co-expressed with ER. Current literature suggests, however, that regardless of tumor type, FOXA1 is an important cofactor for directing the transcriptional activity of AR.


Prostate cancer

Expression of AR with PTEN has also been investigated in prostate cancer. In prostate cancer patients, high AR expression with low PTEN expression is associated with poor clinical outcomes 27 . In prostate tumors, with loss of PTEN, there are decreased levels of AR signaling 28 . Inhibition of PI3K in these tumors results in increased levels of AR signaling through loss of human epidermal growth factor receptor 2 (HER2)-mediated feedback inhibition of AR 28 . A direct physical interaction between AR and PTEN in low passage LNCaP cells has been shown to inhibit nuclear translocation of AR resulting in an increase in degradation of AR protein 29 . A pilot study suggested that high expression of both AR and PTEN in patients with advanced prostate cancer was associated with a higher risk of relapse at 30 months after surgery (85.7% of high AR and PTEN expressing patients verses 16.6% in patients with low AR and PTEN expression) 30 . Further, combination therapy with both antiandrogen (bicalutamide) and PTEN induction was shown to reduce prostate-specific antigen (PSA) promoter activity compared to PTEN alone 31 . Sequencing of metastatic-CRPC (mCRPC) patients revealed that AR and PTEN are among the most commonly aberrant genes, along with the ETS family and TP53 32 . Therefore, these data suggest that both AR and PTEN may influence prostate tumor growth and progression.

Breast cancer

There are opposing findings when comparing AR and PTEN transcript expression in prostate verses breast cancer. In breast cancer, there is an AR-binding motif located in the PTEN promoter, and there is a positive correlation between AR and PTEN transcript levels 27 . In addition, high expression of AR and PTEN is correlated with better clinical outcomes for breast cancer patients 27 . Interestingly, in AR + TNBC, AR interacts at an ARE located in the promoter of ERβ 33 , and ERβ also plays a role in regulation of PTEN expression to control tumor growth 34 . The interaction between AR and PTEN may be context specific and important for predicting outcomes for patients with AR+ disease: where AR expression is associated with disease progression in prostate cancer 7 , PTEN loss is also correlated with poor outcomes 27,35,36 . In breast cancer, however, loss of PTEN is also correlated with negative ER and PR status, and PTEN loss is associated with breast tumor progression 37 . Therefore, these results suggest that the function of PTEN may be context specific and understanding the nuances in situational signaling of AR may help elucidate the role for PTEN in AR+ disease progression.

Non-genomic AR functions

Prostate cancer

Prostate cancer cells exhibit rapid proliferation responses in response to androgen stimulation, suggesting non-genomic AR signaling. Upon activation with androgens or estrogens, cytoplasmic AR can activate MAPK/ERK signaling through an association with Src 38 . The activation of the Src/ERK pathway is dependent on androgen concentration (0.1–10 nM) and is inhibited at high concentrations (100 nM) 39 . Treatment with dihydrotestosterone (DHT) also induces rapid ERK1/2 phosphorylation however, MAPK activation can be blocked pharmacologically using a MEK inhibitor, suggesting AR is activating the Raf1-MEK pathway resulting in MAPK activation 40 . Further, AR can also activate the phosphatidyl-inositol 3-kinase (PI3K)/Akt pathway leading to activation of mammalian target of rapamycin (mTOR) 41 . In addition, androgens can interact at the plasma membrane which is associated with the modulation of intracellular calcium and cAMP levels 41,42 . Many membrane-bound G-protein coupled receptors are also responsive to androgen treatment, leading to an increase in apoptosis 43 , phosphorylation of ERK 44 , or reduced cell migration and metastasis 45 . Together, these findings suggest that AR may also function within the cytoplasm or at the membrane to activate non-genomic functions.

Breast cancer

Similar to non-genomic AR functions in prostate cancer, the cytoplasmic roles of AR have also been investigated in breast cancer. Chia et al. demonstrated that AR is necessary and sufficient for ERK phosphorylation following DHT stimulation in MDA-MB-453 and HCC-1954 cells 46 . Further, inhibition of AR resulted in decreased levels of phospho-Elk1, phospho-RSK, and c-FOS in xenograft tumors and in patient tumors, corresponding to a decrease in ERK target proteins 46 . In TNBC, AR inhibition has also been shown to modulate the activity of the Ca 2+ -activated K + channel, KCa1.1, which is associated with breast cancer invasion and metastasis 47,48 . Multiple groups have also studied the role of cytoplasmic AR phosphorylation 49,50 however, additional work is required to understand how AR modifications influence cellular function and localization. At the membrane, many receptors mediate rapid responses to androgen signaling, representing novel membrane-ARs 51,52 . These signals, however, are complex as agonistic verses antagonistic effects are dependent on receptor stoichiometry 52 . Furthermore, AR is expressed in fibrosarcoma cells however, a significant portion of AR is transcriptionally incompetent and does not bind to AREs upon activation. Rather, there is crosstalk between EGFR and AR, and treatment with bicalutamide decreases xenograft tumor growth 53 . Together these data from multiple cancer models suggest that AR has non-genomic functions affecting tumor growth both in prostate and breast cancer which warrant further investigation.


Effect on development Edit

In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. [15] Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. [16] Testosterone is therefore responsible primarily for the development of male primary sexual characteristics, whilst dihydrotestosterone is responsible for secondary male characteristics.

Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome. [17]

Knockout-mice studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms. [18]

Maintenance of male skeletal integrity Edit

Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes. [19]

Role in females Edit

The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.

Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS). Complete (CAIS) and partial (PAIS) which are a result of mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported. [ citation needed ]

Mechanism of action Edit

Genomic Edit

The primary mechanism of action for androgen receptors is direct regulation of gene transcription. The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene transcription. [20] Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is the insulin-like growth factor 1 receptor (IGF-1R). [21] Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.

One function of androgen receptor that is independent of direct binding to its target DNA sequence is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor, a protein that activates several genes that cause muscle growth. [22]

Androgen receptor is modified by post-translational modification through acetylation, [23] which directly promotes AR-mediated transactivation, apoptosis [24] and contact-independent growth of prostate cancer cells. [25] AR acetylation is induced by androgens [26] and determines recruitment into chromatin. [27] The AR acetylation site is a key target of NAD-dependent and TSA-dependent histone deacetylases [28] and long non-coding RNA. [29]

Non-genomic Edit

More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA. [14] [30] Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.

Gene Edit

In humans, the androgen receptor is encoded by the AR gene located on the X chromosome at Xq11–12. [31] [32]

Deficiencies Edit

The androgen insensitivity syndrome, formerly known as testicular feminization, is caused by a mutation in the androgen receptor gene on the X chromosome (locus: Xq11–Xq12). [33] The androgen receptor seems to affect neuron physiology and is defective in Kennedy's disease. [34] [35] In addition, point mutations and trinucleotide repeat polymorphisms have been linked to a number of additional disorders. [36]

CAG repeats Edit

The AR gene contains CAG repeats that affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists, [37] [38] with African-Americans having fewer repeats than non-Hispanic white Americans. [37] The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.

Isoforms Edit

Two isoforms of the androgen receptor (A and B) have been identified: [39]

  • AR-A – 87 kDa N-terminus truncated (lacks the first 187 amino acids), which results from in vitroproteolysis. [40]
  • AR-B – 110 kDa full length

Domains Edit

Like other nuclear receptors, the androgen receptor is modular in structure and is composed of the following functional domains labeled A through F: [41]

  • A/B) – N-terminal regulatory domain contains: [42]
    • activation function 1 (AF-1) between residues 101 and 370 required for full ligand-activated transcriptional activity
    • activation function 5 (AF-5) between residues 360–485 is responsible for the constitutive activity (activity without bound ligand)
    • dimerization surface involving residues 1–36 (containing the FXXLF motif where F = phenylalanine, L = leucine, and X = any amino acid residue) and 370–494, both of which interact with the ligand binding domain (LBD) in an intramolecular [43][44][45] head-to-tail interaction [46][47][48]
    • activation function 2 (AF-2), responsible for agonist induced activity (activity in the presence of bound agonist)
    • AF-2 binds either the N-terminal FXXFL motif intramolecularly or coactivator proteins (containing the LXXLL or preferably FXXFL motifs) [48]
    • A ligand dependent nuclear export signal[50]

    Splice variants Edit

    AR-V7 is an androgen receptor splice variant that can be detected in circulating tumor cells of metastatic prostate cancer patients [51] [52] and is predictive of resistance to some drugs. [53]

    High expression in androgen receptor has been linked to aggression and sex drive by affecting the HPA and HPG axis [54]

    Aberrant androgen receptor coregulator activity may contribute to the progression of prostate cancer. [55]

    1. ^ At androgen receptors measured in human prostate tissue.
    2. ^ Relative to Metribolone, which is by definition 100%

    Agonists Edit

    Mixed Edit

    Antagonists Edit

    The AR is an important therapeutic target in prostate cancer. Thus many different antiandrogens have been developed, primarily targeting the ligand-binding domain of the protein. [58] AR ligands can either be classified based on their structure (steroidal or nonsteroidal) or based on their ability to activate or inhibit transcription (agonists or antagonists). [59] Inhibitors that target alternative functional domains (N-terminal domain, DNA-binding domain) of the protein are still under development. [57]

    Why hormonal balance is important?

    Hormones play a vital role in the human body as they are responsible for maintaining the daily health. Hormones affect different parts of human body individually and as a result, dramatic changes occur. As hormones are quite influential, so if there is no balance, then this could result in disorders and many other severe diseases in human body.

    Men and women are equally affected due to the imbalance in hormones, but things get crucial for women especially as they have to go through the complexities of reproduction.

    In advanced cancer, your doctor will take a small part of the cancer that has spread to your lymph nodes, liver, or other areas of your body. They may use a very fine needle or get the tissue during surgery. Lab tests will show if the disease has hormone receptors.


    If you're taking hormones, you may need to stop before getting the test.

    • Estrogen receptors only. Your doctor will call these “ER-positive” or “ER+” cancers.
    • Progesterone receptors only. These are “PR-positive,” or “PR+.”
    • Both estrogen and progesterone receptors, which doctors call “hormone-responsive”
    • Neither estrogen or progesterone receptors, called “hormone negative” or “HR-"


    All the implants retrieved after 180 days contained small amounts of the hormone, demonstrating the continuous release of the drug during the experiment.

    The rats treated with testosterone showed normal weight gain during the experiment and developed hypertrophy of the clitoris and more aggressive behavior than the control group (data not shown).

    The morphological alterations observed were similar in rats treated with testosterone propionate or non-esterified testosterone. Microscopic examination showed proliferation of terminal and lateral end buds and acinotubular differentiation in all treated animals after 30 days of treatment. In all lobules there was secretory activity, with dilatation of acini and ducts and accumulation of secretion in the lumen ( Figure 1B and C). The proliferation and secretory activity peaked at 90 days of androgen exposure, as demonstrated by morphologic observation and by the volume density of mammary glands obtained by morphometric analysis ( Figure 2). After 90 days the glands presented areas with different glandular patterns, with some showing acinotubular structures with typical secretory activity and others showing less evident secretory differentiation, with reduction of the secretion accumulated in the lumen. Although the volume density of acinotubular structures did not increase, the acinar cells proliferated, filling the lumen. Several acinotubular structures showed acini with a solid pattern, filled with epithelial cells with small, clear vacuoles in the cytoplasm. The solid patterns of the acini as well as the reduction in secretory differentiation were progressive through 120, 150, and 180 days of androgen exposure ( Figure 1). In all rats killed at 180 days the acinotubular structure had vacuolated cells, but acinar epithelial cells without secretory activity were frequently present ( Figure 1D-F). Most of the acini presented a solid pattern, with vacuolated acinar cells filling the lumen. The nuclear pattern observed in proliferating acinar cells, with dark and clear nuclei, was similar to that observed in normal mammary acini. Epithelial proliferation filling the duct lumen was not observed and the myoepithelial cells apparently were unaffected. There was increased intralobular deposition of collagen after 90 days of androgen exposure ( Figure 1H). Mast cells were frequently prominent in the intralobular stroma with basophilic granules in the cytoplasm ( Figure 1I).

    The proliferation and secretory effects induced by testosterone exposure were similar in all mammary gland pairs. No dysplastic lesions with nuclear pleomorphism or neoplastic lesions were observed in any treated animal.


    1. What are endocrine hormones?
    2. Define the target cell in the context of endocrine hormones.
    3. Explain how steroid hormones influence target cells.
    4. How do non-steroid hormones affect target cells?
    5. Compare and contrast negative and positive feedback loops.
    6. Outline the way feedback controls the production of thyroid hormones.
    7. Describe the feedback mechanism that controls milk production by the mammary glands.
    8. Why do endocrine hormones only affect some of the cells in the body? Choose the best answer.
      1. They only reach certain cells.
      2. Many hormones cannot cross the plasma membrane of cells.
      3. Some cells feedback negatively in response to a hormone.
      4. Only some cells have receptor proteins that can bind to a given hormone.
      1. Prolactin
      2. Insulin
      3. Cortisol
      4. Thyrotropin releasing hormone