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Effects of 5α-Androst-16-en-3α-ol on the pulsatile secretion of luteinizing hormone in human females

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Abstract

We examined the effects of 5alpha-androst-16-en-3alpha-ol (3alpha-androstenol) on pulsatile luteinizing hormone (LH) secretion in human females. The frequency of the LH pulse in the follicular phase was decreased by exposing the women to 3alpha-androstenol.
SHORT REPORT
Effects of 5α-Androst-16-en-3α-ol on the Pulsatile Secretion of Luteinizing
Hormone in Human Females
Kazuyuki Shinohara, Masayo Morofushi, Tosihya Funabashi, Dai Mitsushima and
Fukuko Kimura
Department of Physiology, Yokohama City University School of Medicine, 3–9 Fukuura,
Kanazawa-ku, Yokohama 236-0004, Japan
Correspondence to be sent to: Kazuyuki Shinohara, MD, PhD, Department of Physiology, Yokohama City University School of Medicine,
3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. e-mail: Kazuyuki @ med.yokohama-cu.ac.jp
Abstract
We examined the effects of 5α-androst-16-en-3α-ol (3α-androstenol) on pulsatile luteinizing hormone (LH) secretion in
human females. The frequency of the LH pulse in the follicular phase was decreased by exposing the women to
3α-androstenol.
Introduction
Menstrual synchrony, the convergence of the onset date
of the menstrual flow, is observed in women living to-
gether (Weller and Weller, 1993). Menstrual synchrony has
been shown to be mediated by axillary odour (Stern and
McClintock, 1998). Axillary odours from women in the
follicular phase (FP) of the ovulatory cycle shorten both
the time to ovulation and the length of the menstrual cycle
in the recipients whereas axillary odours in the ovulatory
phase (OP) delay ovulation and lengthen the menstrual
cycle. However, the pheromones in the axillary compounds,
which regulate both the time to ovulation and the length of
the menstrual cycle, have not hitherto been identified.
When we examined the relationship between menstrual
synchrony and the ability to smell a putative pheromone,
5α-androst-16-en-3α-ol (3α-androstenol), the women who
showed menstrual synchrony had a high sensitivity to 3α-
androstenol (Morofushi et al., 2000). It is therefore possible
to speculate that human females use 3α-androstenol to syn-
chronize their menstrual cycles. We recently reported that
axillary compounds in the FP increased the frequency of
pulsatile secretion of luteinizing hormone (LH) and axillary
compounds in the OP decreased it, suggesting that axil-
lary compounds change the length of the menstrual cycle
by changing the frequency of the pulsatile LH secretion
(Shinohara et al., 1999). In the present study, we examined
the effect of 3α-androstenol on the pulsatile secretion of LH
to explore the possibility that 3α-androstenol is one of the
active substances in axillary compounds which regulate the
length of the menstrual cycle.
Materials and methods
Eleven female college students, aged 19–25 years and with a
history of regular ovulation, were involved in this study.
From 10:00 to 18:00 on days 5–7 after the menstrual onset,
blood samples were collected through an i.v. heparin-locked
catheter at 10 min intervals. The subjects took 100 kcal
isocaloric snacks and 100 ml water hourly for 8 h. They were
not exposed to anything for the first 4 h. Afterwards,
2.5 mM 3α-androstenol in 70% isopropyl alcohol (IA)
was applied hourly to half of them by wiping above their
upper lip with a pad containing the solution for the next
4 h. IA alone was applied to the others in a similar way to
3α-androstenol. Blood plasma was separated by centri-
fugation at 2000 g for 10 min and stored at –30°C until the
LH assay (SAPC-S LH RIA kit; Daiichi Radioisotope
Laboratory, Tokyo, Japan). The mean of the minimally
detectable amount of LH was ~0.3 mIU/ml. The intra-assay
coefficients of variation (CV) which were calculated on
the basis of duplicated measurement of pooled samples
containing 7.78 and 42.1 mIU/ml were 4.17 and 0.66%,
respectively. An LH pulse was defined as when both the
ascending and descending CVs were >1.7 times the intra-
assay CV. The protocol observed the tenets of the Declaration
of Helsinki and was approved by the Ethics Committee
of Yokohama City University. The subject gave written
© Oxford University Press 2000
Chem. Senses 25: 465–467, 2000
informed consent after the procedures had been fully
explained.
Results
As seen in a representative subject (Figure 1a), the intervals
between consecutive peaks of pulsatile LH secretion were
70, 70 and 70 min before the application of 3α-androstenol,
but after the start of the application the intervals became
longer: 90 and 80 min. On the other hand, IA alone had no
effect on the interpulse intervals: 60, 60 and 50 min before
IA application and 60, 60 and 60 min during the application
(Figure 1b). The mean SE) interpulse interval between
LH pulses (n = 6) was significantly (P < 0.05, paired t-test)
increased from 53.9 ± 3.9 to 66.0 ± 1.5 min in response to
3α-androstenol. No change in the mean interpulse interval
between LH pulses was observed in response to IA (P >
0.05, paired t-test). The mean interpulse intervals between
LH pulses (n = 5) before IA application and during the
application were 54.0 ± 4.9 and 53.8 ± 4.7 min, respectively.
The data were expressed as the frequency are shown in
Table 1. 3α-Androstenol decreased the frequency while IA
alone had no effect.
Discussion
The present results demonstrate that the frequency of
pulsatile secretion of LH is decreased by exposing women to
3α-androstenol. This finding indicates that 3α-androstenol
retards the growth and maturation of ovarian follicles and
consequently delays the timing of ovulation. It is therefore
possible that 3α-androstenol is involved in menstrual syn-
chrony by increasing the period of menstrual cycles.
3α-Androstenol is known to be secreted from the axillae
in humans (Gower and Ruparelia, 1993). The steroid has
been demonstrated to act as a pheromone in pigs (Gower
and Ruparelia, 1993). It is secreted in the saliva of the
boar and acts as a pheromone effective in eliciting the
characteristic immobilization response of the estrous sow
to the advance of her mate (Gower and Ruparelia, 1993).
(Z)-7-Dodecen-1-yl acetate is used as a pheromone by the
females of more than 126 species of insects and the elephant
(Rasmussen et al., 1996). 3α-Androstenol has been reported
as affecting women’s mood (Gower and Ruparelia, 1993)
and sexual arousal (Gower and Ruparelia, 1993), so it also
may not be a species-specific pheromone.
Furthermore, women whose menstrual cycles became
synchronized with that of room-mates within 3 months had
higher olfactory acuity for 3α-androstenol than non-
synchronized women, suggesting that the ability to perceive
the odour emitted by 3α-androstenol is related to the men-
strual synchrony (Morofushi et al., 2000). We recently
showed that the frequency of the LH pulse was increased by
axillary compounds in the FP, which shorten the menstrual
cycle, and decreased by axillary compounds in the OP, which
lengthen it (Shinohara et al., 1999). Together with these
findings, the present results suggest that 3α-androstenol may
be a pheromone included in axillary compounds secreted in
the OP, which lengthen the menstrual cycle.
References
Gower, D.B. and Ruparelia, B.A. (1993) Olfaction in humans with special
reference to odorous 16-androstenes: their occurrence, perception and
possible social, psychological and sexual impact. J. Endocrinol., 137,
167–187.
Figure 1 Representative examples of the effect of 3α-androstenol (a) and
isopropyl alcohol (b) on pulatile LH secretion.
Ta b le 1 Effects of 3α-androstenol and isopropyl alcohol on the
frequency (the number of pulses/4 h) of LH pulses
3α-Androstenol Isopropyl alcohol
Before application 4.57 ± 0.81 (6) 4.59 ± 0.88 (5)
During application 3.64 ± 0.21 (6) 4.59 ± 0.83 (5)
Data are the mean ± SE. Numbers in parentheses indicate the number of
subjects.
466 K. Shinohara et al.
Morofushi, M., Shinohara, K., Funabashi, T. and Kimura, F. (2000)
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smell 5α-androst-16-en-3α-ol, Chem. Senses, in press.
Rasmussen, L.E.L., Lee, T.D., Roelofs, W.L., Zang, A., and Davis, G.D.
(1996) Insect pheromone in elephants. Nature, 379, 684.
Shinohara K., Morofushi M. and Kimura, F. (1999) Effects of human
pheromones on pulsatile luteinizing hormone secretions. Neurosci. Res.,
Suppl. 23, S233.
Stern, K. and McClintock, M.K. (1998) Regulation of ovulation by human
pheromones. Nature, 392, 177–179.
Weller, A. and Weller, L. (1993) Human menstrual synchrony: a critical
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Accepted May 17, 2000
Effect of 5αAndrost-16-en-3αol on LH Secretion 467
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Effects of human pheromones on pulsatile luteinizing hormone secretions
  • K Shinohara
  • M Morofushi
  • F Kimura
Shinohara K., Morofushi M. and Kimura, F. (1999) Effects of human pheromones on pulsatile luteinizing hormone secretions. Neurosci. Res., Suppl. 23, S233.