Females (birds) cannot reproduce without androgens
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One of Ray’s most memorable quotes is that medicine’s insistence in dividing hormones into “male” and “female” has poisoned the collective scientific mind and negatively affects future studies by precluding a more open-minded view in regards to steroids’ real physiological role – i.e. that of metabolic modulators. While his comments were frequently in regards to the erroneous view of estrogen as a “female” hormone (it is in fact a stress hormone, not unlike cortisol) he also commented in the role of androgens in female health. The study below corroborates Ray’s writings by showing that female birds that lack the androgen receptor (and are thus unable to respond to androgens) are actually infertile (actually, sterile may be a more appropriate label) and cannot reproduce, just like male birds who are also infertile/sterile without androgens. In further support of the crucial role of androgens in female health, several recent humans studies have demonstrated that the infertility associated with menopause may be due to declining levels of the adrenal androgen DHEA, which in women gets metabolized predominantly into the classic “male” hormones testosterone (T) and dihydrotestosterone (DHT). Conversely, supplementation with DHEA increased conception rates in older women by about 40% largely as a result of increasing the levels of the crucial ovarian factor known as Anti-Müllerian Hormone (AMH), which is the main biomarker in females for ovarian reserves. AMH levels decline with age and are undetectable in menopause. The human studies mentioned above showed that adminstration of DHEA raises AMH levels to the point where viable eggs are released and pregnancy can occur in about half of the treated women. Similar results have also been demonstrated with the administration of T in women, thus strongly suggesting that the pro-fertility effects of DHEA are through its conversion in women into classic male hormones such as T. Hopefully, as new studies on androgens continue to be published, medicine will change its ossified view on steroids into something more flexible and beneficial to humans.
https://www.nature.com/articles/s41467-024-52989-w
https://phys.org/news/2024-10-genetically-chickens-reveal-testosterone-complex.html
“…Although testosterone is also present in females and has important functions there, it is classically referred to as the “male hormone”: it significantly contributes to the sexual development, appearance and aggression behavior of males. To exert its function, testosterone binds to the so-called androgen receptor. This is then activated and triggers the production of certain proteins in the cell. However, testosterone can also be metabolized into estrogen—the “female hormone”—which binds to a different receptor. This is where things get complicated: when we talk about testosterone and its effects, what is the role of the androgen signaling pathway? A team of scientists around Benjamin Schusser (TUM) and Manfred Gahr (MPI for Biological Intelligence) has taken a closer look at this question in birds. In a complex undertaking, the researchers used the CRISPR-Cas method to create genetically modified chickens that lack the androgen receptor.”
“…As expected, the examination of the young roosters showed that they were infertile. In addition, some of the typical external sexual characteristics were underdeveloped. These included the comb, wattle and earlaps. Interestingly, other traits remained unaffected by the genetic modification: the tail feathers and the spurs were comparable to normal roosters. “We were surprised to find that the male traits were only partially lost. The outer appearance of roosters is therefore not solely determined by the androgen signaling pathway,” explains Mekhla Rudra, one of the two lead authors of the study. Interestingly, young hens without the androgen receptor showed a very similar picture. They were also infertile and the typical head ornaments were much smaller than normal. As a result, young roosters and hens were almost indistinguishable in appearance—quite unlike chickens that carry the androgen receptor. Surprisingly, although adult females continued to produce testosterone, without the androgen receptors they never lay eggs nor ovulate, showing that egg formation and laying are androgen-dependent. The results show that testosterone plays an important role in both sexes. It is therefore too simplistic to describe it as a pure male hormone. The way the hormone works is complex and not yet fully understood. Additionally, the study provides general insights into the sexual development of birds, which appears to involve a complex interplay of hormone-dependent and hormone-independent mechanisms.”
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@haidut Throwback to this classic thread: The Progesterone-like Action Of Testosterone And Other Androgens
