An idea for research.

[IDW2BB]

Has there ever been a study of the sons of The highest Norwood males? I would think a lot of information could be gleaned from such research. I see a lot of research comparing bald guys to non-bald guys but none about an adolescent son of an Androgenetic Alopecia sufferer. It seems that comparing the two scalp samples of a bald father and a son just before puberty, and then a follow-up every 6 months or so could shed some light on what flips the switch in the worst cases of Androgenetic Alopecia. A lot of research has gone into looking at the condition after it's onset. I don't think enough research has gone on exploring what changes take place in the scalp of a son who is destined to be a high Norwood like his old man. What would be great is if they could get tiny punch samples from 3 generations of high Norwood sufferers and follow up for a good 5-10 years. Genetic and epigenetic testing of the scalp and measuring everything that can be measured. I think this type of research would provide some great information and perhaps answer some questions.

 

[benjt]

could shed some light on what flips the switch in the worst cases of Androgenetic Alopecia

Only under the assumption that there is any "flip the switch condition" to begin with. I assume that there is no flip switched at all in the scalp, i.e. the follicles are prone to androgens for miniaturization right from the start. However, androgen levels only become sufficiently high for that effect once puberty starts (cf. Wikipedia on androgen levels).

If that assumption is correct, then there is likely no difference between the onset of Androgenetic Alopecia where the very first hair follicles (right at the lowest point of "healthy" temples) are hit as compared to follicles of a NW3 being initially hit and miniaturizing once the Androgenetic Alopecia/male pattern baldness has progressed this far.

 

[IDW2BB]

Only under the assumption that there is any "flip the switch condition" to begin with. I assume that there is no flip switched at all in the scalp, i.e. the follicles are prone to androgens for miniaturization right from the start. However, androgen levels only become sufficiently high for that effect once puberty starts (cf. Wikipedia on androgen levels).

If that assumption is correct, then there is likely no difference between the onset of Androgenetic Alopecia where the very first hair follicles (right at the lowest point of "healthy" temples) are hit as compared to follicles of a NW3 being initially hit and miniaturizing once the Androgenetic Alopecia/male pattern baldness has progressed this far.

"Flip the switch" may have been a poor choice of words on my part. I was referring to the condition of the hair and surrounding tissue at the time of puberty. What was the environment and local androgen level once the "gene" was turned on. How is that different than the fathers? I may be wrong, probably am, just seems to me that this type of research could shed some light on the cause vs consequence aspects of Androgenetic Alopecia. At least some of them.

 

[benjt]

While I really appreciate all your contributions, I think this time you are wrong

The gene doesn't get activated, it is - as far as is known - active from the start. And the process right at the onset of Androgenetic Alopecia/male pattern baldness is no different from the process that later on hits hair follicles that hadnt been hit until then, simply because they weren't "in the line of fire" until that point.

The only possible change I could imagine is that the body, when T is first produced in puberty, a) starts producing 5aR and b) increases androgen receptor counts under the influence of T. It#s the only thing I could think of that potentially changes there at all.

 

[Armando Jose]

Has there ever been a study of the sons of The highest Norwood males? I would think a lot of information could be gleaned from such research. I see a lot of research comparing bald guys to non-bald guys but none about an adolescent son of an Androgenetic Alopecia sufferer. It seems that comparing the two scalp samples of a bald father and a son just before puberty, and then a follow-up every 6 months or so could shed some light on what flips the switch in the worst cases of Androgenetic Alopecia. A lot of research has gone into looking at the condition after it's onset. I don't think enough research has gone on exploring what changes take place in the scalp of a son who is destined to be a high Norwood like his old man. What would be great is if they could get tiny punch samples from 3 generations of high Norwood sufferers and follow up for a good 5-10 years. Genetic and epigenetic testing of the scalp and measuring everything that can be measured. I think this type of research would provide some great information and perhaps answer some questions.

Very interesting, easy study btw.

Also, if we can collect the dates of the thickness and density of scalp hairs in persons with Androgenetic Alopecia and No Androgenetic Alopecia, we can probably have a big surprise, because person with high density and thicker hair have less probabilty to suffer common hair loss, ...., easy, .....

 

[bushbush]

we can probably have a big surprise, because person with high density and thicker hair have less probabilty to suffer common hair loss, ...., easy, .....

And what exactly would this tell us?

 

[Armando Jose]

this tell us that in common alopecia the trigger is not the famous androgens.
Then, we can say that persons with thicker hair and high hair density never go bald.
Later, with ideas and investigations we'll find out which is the first step in this multifactorial issue, probably problems with sebum....

 

[uncomfortable man]

Back to the drawing board eh? I'm liable to blow my braains out all over that board. I'm kidding, go back to being productive.

 

[IDW2BB]

Perhaps this method could be used to measure differences in cellular signaling:


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994437/

The cytokine secretion dynamics in monocytes described herein implies that cell-cell communication via cytokines also varies widely with regard to timing. Further studies are required to clarify the manner in which heterogeneous cell-cell communication affects the maintenance of homeostasis of the immune system under various complex physiological situations, such as T-helper subset differentiation27 and the switch from acute resolving to chronic persistent inflammation28. The establishment of the real-time secretion assay platform described in this study opens the way to addressing these issues through the monitoring of cytokine secretion dynamics in parallel with intracellular events at single-cell resolution.

 

[bushbush]

this tell us that in common alopecia the trigger is not the famous androgens.
Then, we can say that persons with thicker hair and high hair density never go bald.
Later, with ideas and investigations we'll find out which is the first step in this multifactorial issue, probably problems with sebum....

Or, you know, they have thicker hair and higher density because they aren't balding in the first place... Correlations do not equal cause and effect.

 

[Armando Jose]

Or, you know, they have thicker hair and higher density because they aren't balding in the first place... Correlations do not equal cause and effect.

No, the idea is measure thickness and density of the hair from the sides of head (the remaining hair in hair loss suffer, which mantain the original characteristics of it). Then we shall encounter a perfect correlation between incidence of common baldness and these parameters. After it is important ask us, why? .... I have the theory that problems with hair fat is the key....

 

[IDW2BB]

While I really appreciate all your contributions, I think this time you are wrong

The gene doesn't get activated, it is - as far as is known - active from the start. And the process right at the onset of Androgenetic Alopecia/male pattern baldness is no different from the process that later on hits hair follicles that hadnt been hit until then, simply because they weren't "in the line of fire" until that point.

The only possible change I could imagine is that the body, when T is first produced in puberty, a) starts producing 5aR and b) increases androgen receptor counts under the influence of T. It#s the only thing I could think of that potentially changes there at all.

@benjt, I have no problem with being wrong! I appreciate discussion and disagreement without nastiness. I just think that the transition of puberty should be further explored. You yourself in another post stated DHT + inflammation are the main focus. Many parts to that. I think there is a sequence we don't understand yet and parts to be discovered.
No better way to follow the sequence and perhaps discover some new parts than to thoroughly monitor a destined Norwood VI. Put some sort of nano chip in the skin to record signaling and what is being produced and when. Do the same for the father and grandfather if possible.

 

[brunobald]

I agree that there is some "flick of the switch event". My reason is because I started losing hair at 26, prior to this I had zero miniaturisation and very little shedding. Then almost overnight I began shedding hairs, up to 700 per day, my scalp was inflamed and itchy and sometimes felt like someone had pored a weak acid on it. Almost overnight I had gone from zero male pattern baldness to aggressive male pattern baldness, yet I was able to grow a strong beard from 14-16 years old so I must have had plenty of dht for over ten years and great hair. My uncle is in a similar position, the only difference is he kept his hair for an extra 20 years.

 

[xRedStaRx]

I agree that there is some "flick of the switch event". My reason is because I started losing hair at 26, prior to this I had zero miniaturisation and very little shedding. Then almost overnight I began shedding hairs, up to 700 per day, my scalp was inflamed and itchy and sometimes felt like someone had pored a weak acid on it. Almost overnight I had gone from zero male pattern baldness to aggressive male pattern baldness, yet I was able to grow a strong beard from 14-16 years old so I must have had plenty of dht for over ten years and great hair. My uncle is in a similar position, the only difference is he kept his hair for an extra 20 years.

High serum DHT = lower chance of alopecia, but high local 5-AR activity = hair loss!

 

[IDW2BB]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998739/


from the link:

Prepubertal hypertrichosis is a poorly understood clinical entity which may cause significant patient and parental anxiety. In this study, we performed an assessment of ovarian function and androgen receptor repeat polymorphisms in a large group of carefully selected prepubertal girls with this condition, which were compared with a group of control girls.

The limited data available regarding the androgen profile of girls with prepubertal hypertrichosis are somewhat controversial. Balducci and Toscano demonstrated elevated concentrations of serum dihydrotestosterone (DHT) in a small group of prepubertal girls with hypertrichosis compared with age-matched controls. These authors, however, did not observe a concomitant increase in the levels of the DHT metabolite 3α- androstanediol glucuronide [12]. Gryngarten et al. observed increased serum testosterone levels and FAI in a group of prepubertal girls with hypertricosis compared to controls. In addition, they observed a slight increase in 3α-androstanediol glucuronide concentrations in approximately half of their girls with hypertrichosis [13].

We evaluated 42 prepubertal girls with hypertrichosis that were matched with 29 control prepubertal girls. We did not observe any differences in the androgen profile of both groups, except for lower levels of SHBG in the girls with hypertrichosis, although FAI was not different. In addition, serum AMH levels and pelvic ultrasound were similar in both groups. We also performed an hormonal study in both groups of girls, but we did not observe any differences in the basal concentrations of gonadotropins or sex steroid concentrations.

The investigation of the androgen receptor repeat polymorphisms provided the most interesting results of this study. Androgen receptor CAG repeats usually range between 11 and 35, and a decreased CAG repeat number has been linked to an increased transcriptional response to androgens [25]. Van Nieuwerburgh et al. studied 97 oligo-anovulatory women with ultrasound features of PCOS, and observed that patients with a bi-allelic mean lower than 21 repeats had lower androgen levels, but more florid clinical evidence of acne and/or hirsutism [26]. Ibañez et al. observed that girls with precocious pubarche had shorter mean CAG repeats and a greater proportion of short alleles (20 repeats or less) compared to controls. They concluded that shorter androgen receptor CAG number is indicative of increased androgen sensitivity, and subsequent ovarian hyperandrogenism [27]. In addition, Vottero et al. reported a reduced androgen receptor gene methylation pattern, which was associated with the presence of shorter CAG repeats, in girls with precocious pubarche. This constellation of findings might lead to hypersensitivity of the hair follicles to androgens, and therefore to the premature development of pubic hair [28].

On the other hand, in vitro characterization has showed a higher transactivating capacity for GGN 23 allele (GGC 17), and GGN 27 or GGN 10, compared to GGN 24 with a constant CAG repeat number of CAG 22, in response to testosterone analogs (R1881) and 5-α dihydrotestosterone. In accordance with several reports, our GGC distribution showed that GGC 17 and GGC 18 were the most frequent alleles in our population.

In the present study we did not find differences in the mean number of CAG or GGC repeats. In order to investigate the combined contribution of the CAG and GGC alleles to androgen sensitivity, we performed a study of the joint distribution of these alleles. The combined analysis of CAG/GGC showed a significantly higher prevalence of the most androgen-sensitive combinations (<18 CAG+17/17 GGC and <14 CAG+17/18 GGC) in the girls with hypertrychosis. The normal androgen levels in haplotypes 1 and 2 indicates that they may develop hypertrichosis due to enhanced androgen receptor sensitivity. The higher AMH and inhibin B levels observed in these patients, suggests that they appear to have a higher number of small antral follicles, as observed in patients with PCO. In addition, the girls who harbored combinations 3 – 5 had lower SHBG concentrations compared to controls. This hormonal pattern may lead to the development of hypertrichosis due to a higher free androgen index. The lower LH levels observed in these patients may be consequence of the central negative feedback by androgens.

Although it is known that analyzing blood DNA may not reflect target tissue AR sensitivity, we did not perform skin biopsies to study AR sensitivity due to ethical considerations.

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http://www.sciencedirect.com/science/article/pii/S1873506114000415

Discussion

Epithelial proliferation is concentrated at the tips of the developing prostate ducts and early studies focused on the duct tip as the probable site of progenitor/stem cells (Kinbara et al., 1996). Subsequent studies examining label retention and regenerative capacity implicated the proximal duct as the reservoir of stem/progenitor cells in the adult prostate (Tsujimura et al., 2002, Kinbara et al., 1996, Burger et al., 2005 and Xin et al., 2005). Further studies sorting for putative stem cell markers and testing for regenerative potential confirmed a relative abundance of stem cells in the proximal duct as compared to the intermediate and distal duct segments (Evans and Chandler, 1987, Lawson et al., 2007, Burger et al., 2005 and Xin et al., 2005). Labeling with either BrdU or GFP at the onset of ductal budding yielded a small population of labeled cells in the adult prostate concentrated in the proximal ducts near their urethral origin. In our study, we also observed label-retaining stromal cells localized to the stromal compartment surrounding the proximal ducts. This could be coincidence, but it does suggest the possibility that slow-cycling epithelial and stromal cells are co-localized within a specific niche in the adult gland and share regulatory signaling mechanisms (Goto et al., 2006, Potten and Loeffler, 1990 and Lavker and Sun, 2000). The most striking findings were robust proliferation of these cells at E16, the preponderance of AR gene expression and the proliferative response to castration.

The ducts of the adult mouse prostate are lined by a pseudostratified epithelium composed of basal cells, luminal cells and rare neuroendocrine cells. The identity and location of stem cells within this epithelial layer are still a matter of debate. At one time basal cells were widely believed to contain progenitor cells capable of differentiating into basal, luminal and neuroendocrine cells (Collins et al., 2001 and Wang et al., 2001). This view has been challenged by recent observations suggesting that stem cells may also reside in the luminal cell layer (Slack, 2000). Single cells co-expressing the markers used in our studies (Lin− Sca-1+CD133+CD44+CD117+) have been shown capable of regenerating a fully differentiated prostate epithelium (Leong et al., 2008). We found that GFP label retaining cells were enriched for co-expression of Lin− Sca-1+CD133+CD44+CD117+. While only a fraction of label retaining cells co-expressed the four stem cell markers, they accounted for approximately a quarter of all the cells co-expressing these markers. This was unexpected and suggests that initiation of prostate ductal budding is associated with a uniquely robust proliferation of epithelial stem/progenitor cells. This is to our knowledge the first evidence that initiation of prostate organogenesis is accompanied by a burst of proliferation among cells that will become a tissue specific stem or progenitor cells in the adult organ. We speculate that this proliferative burst potentially creates a window of vulnerability of these reserve cells to mutation or imprinting changes that could predispose to neoplasia in the adult. Whether a similar burst of proliferation among stem/progenitor cells in other developing organs remains to be determined.

AR is present in the nucleus of most epithelial and stromal cells of the intact adult prostate. Luminal cells are predominantly, if not exclusively, androgen positive whereas only half of all basal cells are (Wang et al., 2009). AR in the stroma mediates paracrine stimulation of epithelial proliferation while AR in epithelial cells stimulates luminal cell differentiation and protein synthesis. It has been assumed that prostate stem cells lack AR (Mirosevich et al., 1999); however, there is some evidence to challenge this view as it applies to the human prostate (Oldridge et al., 2012) and the mouse prostate (Slack, 2000). We found that most BrdU label retaining epithelial cells in the adult prostate were AR positive. More striking was the observation that four-marker positive cells are nearly all AR positive. Insofar as previous studies showed that 14 in 97 four-marker positive cells exhibit the regenerative capacity bona fide stem cells in a tissue recombination assay (Leong et al., 2008), our data suggests that at least some, if not all, stem cells are AR positive.

AR has been shown to exert a growth inhibitory effect in luminal cells. In transgenic mice lacking epithelial AR, epithelial cells are less differentiated and hyper-proliferative (Heer, 2011). It is possible that selective proliferation of slow-cycling and 4-marker cells after castration reflects a release of androgen-mediated inhibition of proliferation of cells that do not require androgen for survival. There is precedent for this in the breast where estrogen suppresses stem cell proliferation (Wu et al., 2007). An alternative explanation for proliferation and migration of LRCs and 4-marker cells following castration would be the response to injury. Progenitor cells play a primary role in the regenerative response to injury in a variety of adult tissues (Simões et al., 2011, Amcheslavsky et al., 2009, Imitola et al., 2004, Brunt et al., 2010 and Zhang et al., 2000) and it has been postulated that factors released by injured tissues stimulate stem cell proliferation and attract stem cells to the sites of injury (Crosnier et al., 2006 and Inui and Sakaguchi, 1992). The effects of castration on the adult prostate are a combination of ischemic injury due to vascular disruption, epithelial apoptosis and acute inflammation (Bodine, 1995, Hayek et al., 1999 and Kerr and Searle, 1973). Whether a direct response to decreased testosterone levels or in response to castration-induced injury, our observation may be relevant to the behavior of tumor stem cells in prostate cancer. To the extent that tumor stem cells phenocopy the features of normal adult stem/progenitor cells, our findings suggest that treatment of human prostate cancer with androgen deprivation could inadvertently produce an expansion of tumor stem cells.

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http://www.ncbi.nlm.nih.gov/pubmed/14789983

 

[supermusic]

this tell us that in common alopecia the trigger is not the famous androgens. Then, we can say that persons with thicker hair and high hair density never go bald. Later, with ideas and investigations we'll find out which is the first step in this multifactorial issue, probably problems with sebum....

I know severa peolple with thicker and hight hair density that has come to suffer alopecia. Also know people with very fine hair that are not affected.

 

[bushbush]

I know severa peolple with thicker and hight hair density that has come to suffer alopecia. Also know people with very fine hair that are not affected.

Yeah, original hair characteristics have nothing to do with the onset of male pattern baldness.

 

[Armando Jose]

Is it possible any photo?
Many people say that people with dense and thick hair can mantain it more time.... but it is easy measure these items in order to know better.

 

[supermusic]

Is it possible any photo?
Many people say that people with dense and thick hair can mantain it more time.... but it is easy measure these items in order to know better.

super thick hair finally going bald:


Thin and greasy hair that has been maintained over time:



:

 

[Python]

I wonder how john travolta is getting money now days. Since he lost his hair, he gets no movie gigs, so sad.