jvkohl
01-15-2002, 08:22 PM
In another thread I mentioned difficulty in study design. This might give you an idea of what was considered before secondary testing with RONE was initiated, and how the dosage was established. This is pretty technical stuff, but may be of interest to some of the scientifically curious among you. It\'s from a university chemist who was a consultant for a 1999 study.
GOOD NEWS! I hope you can use these arguments below with the Human
Subjects Committee. I should let you know that I will not be able to do
any more work on this next week. I am 30-40 hours behind on a reassigned
project for which I will be making a marathon effort to compensate next
week. However, I think the information below will be extremely useful to
you in justifying your project to the Committee. Check with James Kohl, but
I think an aliquot containing 1 mg of androsterone will be a good maximum
amount of the steroid. How much to consider for a low dose, I\'m not sure:
perhaps 0.1 to 0.5 mg.
I am confident about the following details about androsterone:
Androsterone is a by-product (intermediate) of the metabolism of
testosterone (formed in both men and women). For years it has been known
to be formed in the prostate, breast, ovary, adrenal gland, and the liver.
It is a by-product on its way to being excreted in urine as a
water-soluble conjugate with glucose or sulfate. Before conjugation, the
androsterone, a ketone form, is converted to alcohol forms. The glucose
or sulfate conjugates of these alcohol forms have no known biological
activity. I cannot find any indication of any natural biological activity
of this steroid; again, indications are that it is a \"degradation\" product
that is on its way to excretion. While the liver has been known as the
main site for conjugation of steroid alcohol products to glucose, a recent
report indicates there is an enzyme in human prostate, breast, AND SKIN
which can carry out the conjugation to glucose.
Analysis and further considerations:
1. This background information and other work suggests that
any androsterone absorbed into circulation will be converted to the
alcohol forms and conjugated with glucose, thereby targeting it for
excretion. From the areas of contact, if it is absorbed through tissues,
the androsterone might be expected also to be carried into the liver by
the lipoproteins of the blood system.
2. Because it is an organ with such a large volume, the skin
is an important site of steroid hormone biosynthesis. I have been unable
to find any information about the reverse conversion of androsterone into
a androstendione, species which might end up as estrone or possibly be
reconverted into testosterone. Therefore absorption through the skin does
not seem likely to generate active steroid hormones in the body. Since
there are enzymes in the skin that can convert the androsterone to alcohol
forms and on to conjugated forms with glucose, it is likely that the fate
of the androsterone, if applied to the skin, is excretion.
3. All of these data suggest that the inhalation of small
amounts of androsterone, or absorption into the skin, both from a facial
mask are unlikely to lead to metabolically significant amounts of products
in the steroid synthetic pathways or to have any other fate than
excretion.
4. A simple calculation shows that if 1 mg (= 0.001 g) of
androsterone (MW = 290.4 g) were to be injected into the blood of a person
with 4 L of serum and to be distributed evenly, the serum concentration
would be about 0.7 5M. The sulfate conjugate is found in serum at about 1
to 3 5M (this calculation may come out poorly through Pine Mail): 0.001 g
x 1 mol/290.4 g x 1/4 L = 6.9 x 10-7 M or 0.69 5M (1 5M = 10-6 M). It is
highly unlikely that a significant portion of a 1 mg portion of this
steroid on a bacterial or dust mask could be absorbed through the skin,
sinus, or lung airways. It is a high melting solid that sublimes with
difficulty except under high vacuum. Any serum levels of the steroid
resulting from inhalation or minor contact with the skin would be expected
to result in very small amounts added to serum.
---------------------
All of the above simply attests to the likelihood that no harm would be done via testing with 1mg/ml androsterone. There\'s much more to the story, but I am trying to build a synopsis for a general audience that may help in choices of products containing NONE; OL; RONE or combinations of these compounds. Since I know the most about RONE, and have not directly tested any other compounds, it became my choice for the basis of Scent of Eros. OL was included because it has been shown to affect hormones. The fragrance choice (given samples from the perfumer) was as much luck as anything for me, but it turned out to be an excellent choice due to the involvement of Bruce and the perfumer.
GOOD NEWS! I hope you can use these arguments below with the Human
Subjects Committee. I should let you know that I will not be able to do
any more work on this next week. I am 30-40 hours behind on a reassigned
project for which I will be making a marathon effort to compensate next
week. However, I think the information below will be extremely useful to
you in justifying your project to the Committee. Check with James Kohl, but
I think an aliquot containing 1 mg of androsterone will be a good maximum
amount of the steroid. How much to consider for a low dose, I\'m not sure:
perhaps 0.1 to 0.5 mg.
I am confident about the following details about androsterone:
Androsterone is a by-product (intermediate) of the metabolism of
testosterone (formed in both men and women). For years it has been known
to be formed in the prostate, breast, ovary, adrenal gland, and the liver.
It is a by-product on its way to being excreted in urine as a
water-soluble conjugate with glucose or sulfate. Before conjugation, the
androsterone, a ketone form, is converted to alcohol forms. The glucose
or sulfate conjugates of these alcohol forms have no known biological
activity. I cannot find any indication of any natural biological activity
of this steroid; again, indications are that it is a \"degradation\" product
that is on its way to excretion. While the liver has been known as the
main site for conjugation of steroid alcohol products to glucose, a recent
report indicates there is an enzyme in human prostate, breast, AND SKIN
which can carry out the conjugation to glucose.
Analysis and further considerations:
1. This background information and other work suggests that
any androsterone absorbed into circulation will be converted to the
alcohol forms and conjugated with glucose, thereby targeting it for
excretion. From the areas of contact, if it is absorbed through tissues,
the androsterone might be expected also to be carried into the liver by
the lipoproteins of the blood system.
2. Because it is an organ with such a large volume, the skin
is an important site of steroid hormone biosynthesis. I have been unable
to find any information about the reverse conversion of androsterone into
a androstendione, species which might end up as estrone or possibly be
reconverted into testosterone. Therefore absorption through the skin does
not seem likely to generate active steroid hormones in the body. Since
there are enzymes in the skin that can convert the androsterone to alcohol
forms and on to conjugated forms with glucose, it is likely that the fate
of the androsterone, if applied to the skin, is excretion.
3. All of these data suggest that the inhalation of small
amounts of androsterone, or absorption into the skin, both from a facial
mask are unlikely to lead to metabolically significant amounts of products
in the steroid synthetic pathways or to have any other fate than
excretion.
4. A simple calculation shows that if 1 mg (= 0.001 g) of
androsterone (MW = 290.4 g) were to be injected into the blood of a person
with 4 L of serum and to be distributed evenly, the serum concentration
would be about 0.7 5M. The sulfate conjugate is found in serum at about 1
to 3 5M (this calculation may come out poorly through Pine Mail): 0.001 g
x 1 mol/290.4 g x 1/4 L = 6.9 x 10-7 M or 0.69 5M (1 5M = 10-6 M). It is
highly unlikely that a significant portion of a 1 mg portion of this
steroid on a bacterial or dust mask could be absorbed through the skin,
sinus, or lung airways. It is a high melting solid that sublimes with
difficulty except under high vacuum. Any serum levels of the steroid
resulting from inhalation or minor contact with the skin would be expected
to result in very small amounts added to serum.
---------------------
All of the above simply attests to the likelihood that no harm would be done via testing with 1mg/ml androsterone. There\'s much more to the story, but I am trying to build a synopsis for a general audience that may help in choices of products containing NONE; OL; RONE or combinations of these compounds. Since I know the most about RONE, and have not directly tested any other compounds, it became my choice for the basis of Scent of Eros. OL was included because it has been shown to affect hormones. The fragrance choice (given samples from the perfumer) was as much luck as anything for me, but it turned out to be an excellent choice due to the involvement of Bruce and the perfumer.