Androsterone
It is believed that a deficiency
of androgens, including free testosterone, may promote the development of
convulsions. The present study revealed differences in the action of
androsterone (AND), a major excreted metabolite of testosterone and a
neurosteroid, in three commonly used seizure models in mice. AND administered
intraperitoneally exhibited dose-dependent protection against tonic-clonic
convulsions caused by maximal electroshock (MES) with ED50
(effective dose50) of 227 mg/kg. The compound also inhibited
the convulsive action of pentylenetetrazole (PTZ), increasing its CD=
(convulsive dose50) for clonic convulsions from 77.2 (PTZ + saline)
to 93.9 (p < 0.05) for PTZ +AND40 mg/kg and 113.9 mg/kg
(p < 0.001) for PTZ +AND60 mg/kg. In mice pretreated with
60 mg/kg AND, the CD50 for PTZ-induced tonic convulsions
increased from 102 to 127.6 mg/kg (p < 0.01) (Mróz,
Katarzyna et al.,2009).
Intraperitoneal injection of 5 α,3α -A–protected mice in a
dose-dependent fashion from seizures in the following modls (ED50, dose in
mg/kg protecting 50% of animals): 6-Hz electrical stimulation (29.1),
pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and aximal electroshock (224). 5β,3α-A also was
active in the 6-Hz and pentylenetetrazol models, but was less potent (ED 50 v alues,
76.9 and 139 mg/kg, respectively), whereas epiandrosterone (5α ,3 β -A) was
inactive (ED 50 , ≤ 300 mg/kg). 5 α ,3 α -A (10–100 μ M ) also inhibited
epileptiform discharges in a concentration-dependent fashion in the in vitro
slice model, whereas 5β ,3 α -A was active but of lower potency, and 5 α ,3 β -A
was inactive (Kaminski et al.,2005).
This
sexual pheromone was first discovered in 1931 by scientists in Germany. Relatively high androsterone value is associated
with sexual preference for females by either sex, whereas a relatively low
androsterone value is associated with sexual preference for males by either sex
(James V. Kohl,2006). The effects of the
androgenic hormone, androsterone sulfate, a 17-ketosteroid, on long term
potentiation in the dentate gyrus (DG) of urethane anesthesized rats were reported.
Intravenous injection of 10 mg of the hormone dissolved in Nutralipid produced
a significant increase of the population spike (PS), but not of the excitatory
post-synaptic potentials (EPSP). The results are discussed in terms of the
potential enhancement that androsterone sulfate may have on memory as was
described for one of its parent compounds, dehydroepiandrosterone (DHEA) and
its potential use as an antidepressant (Urbanoski et al.,2000) .
Androsterone sulfate
(5α-androstan-3α-ol-17-one, 3-sodium sulfate) administered to freely moving
rats via cerebroventricular cannulae induced analgesia, wet-dog shakes, body
jerks, rigidity, Straub tail, hypermotility, excessive grooming,
hyperreactivity to stimuli, aggression, escape behavior, EEG spiking, and behavioral
and EEG seizures. These responses resemble those produced by certain opiate
drugs and by beta-endorphin, an endogenous peptide; they appear during the
5-min infusion period, persist in some cases for several hours, and are
diminished by pretreatment with the narcotic antagonist naloxone (LaBella et al1978).
Both drugs favourably
decreased platelet stickiness (p <000l),but the effect with clofibrate and bandrosterone
(atromid) was more marked than with clofibrate alone (atromid-S). Both drugs. The
effects of clofibrate with and without androsterone on platelet stickiness and the
blood produced a statistically significant (p <Ol001) and similar fall in serum
cholesterol; their effects on low density lipoprotein were inconstant. The changes
in platelet stickiness and in the lipids appeared to be independent (Carson et al.,1966). Androsterone administered
orally to 13 men with coronary heart disease in a dosage of 100 mg. daily for
one month had practically no clinical or serum lipidshifting effects. In
contrast, androsterone given intramuscularly to 8 men in a dosage of 50 mg.
daily for one to four weeks resulted in a significant decrease in the levels of
serum triglycerides and phospholipids, as well as total cholesterol, reflecting
a reduction in the β-lipoprotein fraction. Despite this decrease, the frequency
of local and systemic side-effects renders this compound unsuitable for routine
clinical use. Androsterone was excreted in the urine chiefly as the glucuronide
(Cohen et al.,1961).
The effects of
androsterone and testosterone propionate on atheroma and plasma lipid shifts
induced by cholesterol feeding in cockerels were compared. Both compounds
produced significant inhibition of coronary arterial atheroma. Aortic
atherogenesis was not affected. The effects on plasma lipids were similar;
non-significant reduction in cholesterol (C), significant decrease in
phospholipid (P) with elevated C/P ratios (Cook,1960).
The preputial glands of the hypophysectomized rat grow in response to steroids
possessing the same molecular features which evoke growth in the prostate.
Unlike the prostatic glands of the female rat, the preputial glands are
constantly present. These giant sebaceous glands are useful indicators in the
biological assay in the female rat of steroids with androgenic activity. There
are important synergistic relationships between steroids and pituitary proteins
in the promotion of growth so that hypophysectomy is necessary for the precise
characterization of growth as induced by steroids ( Huggins et al.,1955).
Studied the modifying
effects on the hypoplasia of organs of three hormones—thyroid, androsterone,
and estradiol—given alone or simultaneously. The evidence indicates that the hypoplasia
can be prevented, at least for a certain period of time, by administration of
one or more of these hormones, thyroid and estradiol being particularly effective
(Korenchevsky and Jones, 1946).
With oestradiol dipropionate
alone, the vagina was restored to
normal or supernormal weight, with normal (usually " oestrus ") structure,
but not even a weekly dose of 0*2 mg. was able to produce normal size and weight
of the uterus, although this dose caused pronounced pathological changes
in the structure of this organ. 3. The weak effects of androsterone and transdehydroandrosterone
on the uterus were not significantly increased, as compared within experiments of
shorter duration, but the vagina and especially the preputial glands were considerably
hypertrophied (Korenchevsky et al.,1939).
The
observed results demonstrate that daily injections of 0.5 to 3 mg. of
testosterone in sesame oil and of 3.0 to 5.0 mg. of androsterone in sesame oil
into normal mature female rats leads to a suppression of the oestrous cycles,
as expressed by the vaginal smear, during the 16-day period of injection (Browman,1937).
References:
Browman, Ludvig G.1937.Effects of
androsterone and testosterone on oestrous cycle of rats. Experimental Biology and Medicine 36(2):
205-208.
Carson, P., L. McDonald, S. Pickard,
T. Pilkington, B. Davies, and F. Love.1966. Effects of clofibrate with
androsterone (atromid) and without androsterone (atromid-S) on blood platelets
and lipids in ischaemic heart disease." British heart journal, 28(3): 400.
Cohen, William D., Norio Higano, Roger
W. Robinson, and Raoul J. Le Beau.1961. Changes In Serum Lipids And Urinary
Ketosteroids During Oral And Intramuscular Administration Of Androsterone. The
Journal of Clinical Endocrinology & Metabolism 21(10):1208-1217.
Cook, Donald L.1960. Effects of
androsterone on atherogenesis and plasma lipids in cockerels." Experimental Biology and Medicine 105(3):
586-588.
Huggins, Charles, Frank M. Parsons,
and Elwood V. Jensen.1955. "Promotion Of Growth Of Preputial Glands By
Steroids And The Pituitary Growth Hormone, Endocrinology
57(1):25-32.
James V. Kohl. 2006.The Mind's Eyes: Human Pheromones,
Neuroscience, and Male Sexual Preferences.Journal of Psychology and
Human Sexuality., 18;4:313-369.
Kaminski, Rafal M., Herbert Marini,
Won‐Joo Kim, and Michael A. Rogawski.2005.
Anticonvulsant activity of androsterone and etiocholanolone." Epilepsia 46(6): 819-827.
Korenchevsky, V., and Vera E. Jones.1946.
The Effects of Androsterone, Oestradiol and Thyroid Hormone on the Artificial
Premature “Climacteric” of Pure Gonadal Origin Produced by Ovariectomy in Rats
I. Effects on Weights of Organs. Journal
of gerontology, 1(3 Part 1): 319-335.
Korenchevsky, V., K. Hall, and R.
Burbank. 1939."The manifold effects of prolonged administration of sex hormones
to female rats." Biochemical
Journal,33(3): 372.
LaBella, Frank, Viktor Havlicek,
Carl Pinsky, and Leonid Leybin.1978.Opiate-like, naloxone-reversible effects of
androsterone sulfate in rats. Canadian
journal of physiology and pharmacology 56(6): 940-944.
Moore, Carl R., and Price Dorothy.1937.Some
Effects Of Synthetically Prepared Male Hormone (Androsterone) in the Rat. Endocrinology
21(3): 313-329.
Mróz, Katarzyna, Tomasz Mróz, Marian
Wielosz, and Piotr Tutka.2009.Effects of androsterone on convulsions in various
seizure models in mice." Pharmacological
Reports 61(3): 564-569.
Urbanoski, Karen, John Harris, Karel
Gijsbers, and Bernardo Dubrovsky.2000. Androsterone sulfate increases dentate
gyrus population spike amplitude following tetanic stimulation. Physiology & behavior 71(5):
435-440.
