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Hormones in Context:
Estrogens and Androgens

 

 
We now turn to two examples of feedback systems - one negative, one positive.

The negative feedback system.

Androgens and estrogens are collectively known as gonadotrophins by virtue of the fact that the testes and ovaries are the main sites of production. In both males and females the hypothalamus and the pituitary gland are closely linked in nervous and endocrine communication, in this case by peptide hormones called Gonadotrophin Releasing Hormones.

The pituitary gland produces LH (luteinising hormone) and FSH (follicle stimulating hormone) which stimulate the gonads in two ways:

FSH stimulates growth of the sex cells, the ovarian follicles in a woman, the seminiferous tubules and early stages of sperm production in a man. LH in a woman, in high concentration, induces ovulation in a Graafian follicle which has been primed with FSH.

Negative feedback system  

In addition, LH and FSH stimulate the production of testosterone (primarily) by the testes in a man, estrogens by the ovaries in a woman. It should be noted that they are also produced in small quantities by the adrenal cortex.

Negative feedback operates on the hypothalamus and pituitary, to reduce the output of the pituitary, in response to the overall levels of all gonadal steroids, which are controlled at different levels in men and women.

In adult males the concentration is about 240mg/100ml, about eight times higher than in adult females. However, only about 2% is free and biologically active. The rest is bound to blood protein, some to albumin which are relatively free and the rest to SHBG which provides a store. It is important, then, when reading accounts of hormone concentration, to be sure which testosterone is being considered. In women, the quantity is about 30mg/100ml, of which about 1% is free. Androgens in women are mainly present as androstenedione, which has a number of functions, but testosterone and dihydrotestosterone can be synthesised from it as needed.

Female positive feedback.

The feedback system described in the last section is a homeostatic mechanism for both sexes. In women it is interrupted by a period each month when LH goes into positive feedback, as part of the menstrual cycle.

Day one is typically taken as the last day of menses.

Effectively, initially, the set point is increased and the concentration of FSH and LH gradually rises, when growth starts of a new Graafian follicle in the ovary. The latter begins to secrete estradiol 17ß, androstenedione and a precursor of progesterone.

This increase in steroid levels causes FSH to fall. However, LH begins to stimulate the pituitary, instead of inhibiting it. Note that the feedback system previously described, compensates for loss of steroids. It cannot deal with increases from other sources and, at about day 16, LH and estradiol go into positive feedback, causing a rapid rise, causing the ripe follicle, now a mature ovum, to be released into the Fallopian tube.

The follicle, at this point becomes a corpus luteum, which generates progesterone as well as estradiol. This terminates the positive feedback and initiates another negative feedback system by which LH production by the pituitary is inhibited., Within a day, LH drops rapidly to its normal level.

Estradiol having fallen away, it begins to rise again, along with progesterone, in preparation for pregnancy. In the last few days before menstruation, if the egg has not been fertilised, the corpus luteum regresses, and both fall away to their base levels. There is also a gradual rise and fall in testosterone, peaking at about 17 days.

If the egg is fertilised, the corpus luteum is preserved.

Conversion to estrogen.

It is this process and the production of male sperm, of course, that causes these hormones to be referred to as the sex hormones. However, testosterone is one of a number of androgens. Both androgens and estrogens are involved in a great many other processes. 

Estrogens and androgens are not uniquely male or female. What differs is the ratio between the two sexes. Both seem to be required in both sexes to achieve sexual maturity. Both are produced by the ovaries or testes, and by the adrenal cortex.

COMMENT
Estrogen vital
for male fertility

 
A base level of testosterone in men is needed for spermatogenesis and for prostate and seminal vesicle action. However recent work suggests that a high level of estrogen is also required within the testes to regulate the concentration of sperm in the semen.(1)

COMMENT
The Estrogen
Provocation Study.

 
In men the main circulating androgen is testosterone. Estrogen is present in small amounts, and can be synthesised from testosterone at the point where it is needed. Progesterone is present only as a trace.

In women, androgens are present, principally as androstenedione, which can be converted to testosterone and dihydrotestosterone as needed.

 
To summarise, then, negative feedback senses the total complement of the gonadotrophins of whatever kind, causing the hypothalamus and pituitary to reduce the output of FSH and LH and, in women, periodically, a positive feedback system is superimposed.

 

Role in general metabolism.

Looking once more at the feedback diagram at the beginning of this piece, it would seem that sperm production in men is controlled by LH concentration rather than testosterone. If fertility is the criterion of maleness, one might expect that testosterone is not absolutely essential. Similarly, in the presence of exogenous (from without) hormones, which would cause FSH production to fall, one might expect sterility to be an early result. This was an initial worry when men were prescribed estrogens for various conditions. In fact, it seems remarkably difficult to prevent sperm production, hence the difficulties in developing a male contraceptive pill, without using the dangerously high doses used illegally by certain athletes.

What role does testosterone have for men? It turns out that it isn't an easy question to answer. The consensus opinion seems to be that testosterone is largely concerned with sexual appetite, the reduction of which, for some gender dysphoric people, is a welcome relief. Bancroft(2) points out that one must distinguish this from sexual interest, as mainly cognitive. As regards sexual performance, erection and climax is organised by the peripheral nervous system. On the other hand, lack of testosterone does seem to be associated with reduced seminal emission. Clearly, though, without an appetite for sex, one's level of interest is not likely to be high, and performance will be unenthusiastic.

Androgens and estrogens are concerned in the development and maintenance of secondary sexual characteristics, such as breasts, external genitalia, body hair distribution and so on. Male pattern baldness is to some extent determined genetically, and may be countered in women by the presence of estrogens.

However preoccupied the TG community is with androgens and estrogens, they seem to have little interest for endocrinologists. There is very little about them in the textbooks, and Rose(3) in his book The Chemistry of Life barely mentions them at all.

Complicating the issue is the fact that there is actually a family of different estrogens and androgens, which may be converted from one to another at the point of action.

They play a part in organisation, as for instance modifying development in a male or female direction. Some such developments may remain dormant during childhood. They are to be the source of activation in puberty, though this may be an oversimplification.

Hormones may simply moderate other metabolic processes, perhaps stimulating certain modes of behaviour. Clues to their activity may be gained from the presence of receptors on various organs.

But, in addition, cells develop particular biochemical environments and develop within those environments. In relation to accounts of effects on mood, and on gender identity, the cells of the brain are not excepted.

COMMENT
Estrogen and the
Aging Brain

Recent work has also indicated that estrogens may counter some of the degenerative conditions of the brain which occur with old age. Since the cells concerned do not have receptors for estrogen, it would seem to be a function of the biochemical environment.

COMMENT
Role for estrogen
in bone marrow

The role in bone metabolism of estrogens is fairly well- known, in that one of the benefits of hormone replacement therapy for women is the prevention of osteoporosis. There is a feeling among some workers that an excess above the normal physiological quantity, as when male-to-female transsexuals are prescribed estrogen therapy, may result in bone metabolism being retarded, though they warn that more work needs to be done.(4)

One of the more alarming tests (for mothers) that are performed on new born babies is to manipulate their legs to look for signs of congenital hip dysplasia, a weakness of the thigh bone's joint with the hip.

There is an interesting interaction of genes, sex and environment here, which puzzled researchers for many years. It became clear that the predisposing factor is an inherited geometry of the joint but why was there such cultural variation and why were girls affected more often than boys?

It turned out that, near the moment of birth, the mother's estrogen rises greatly, assisting the articulation, or spreading, of her pelvis to facilitate the process. Some of this estrogen enters the bloodstream of the baby. For a while after birth, the baby's cartilage is also elastic, so that, with this geometry, the hip is more likely to pop out of joint.

The problem was more prevalent in cultures that swaddle their babies tightly. If the baby is allowed to keep its legs in a natural position and exercise them, the joint soon strengthens.

Although testosterone levels are higher in boys at birth, it seems that boys' cartilage is less plastic under the influence of estrogens, which accounts for the difference.

The role that testosterone plays during prenatal development has already been described. In childhood, the concentration of hormones is much the same both sexes. Therefore social theorists assert that any differences in behaviour must be due to upbringing.

The biological school insist that the organisational effects extend to the brain. Some go further and suggest that, when born, children are 'pre-wired' as boys or girls.

They suggest that cognitive changes in puberty arise from such organising effects being activated by hormone changes, rather than changes in the educational curriculum and changing social expectations.

In the extreme, it is suggested that there is no point in trying to rectify social factors behind closing-time pub brawls and joy-riding, even rape and child abuse, because it is written indelibly in human biology. Similarly, women are only fit for rearing children and having the supper ready for when hubby comes home from work. Although there is plenty of literature about the effects of this supposed wiring, no one has really shown how it works, still less that it somehow 'tells' a child it is a boy or a girl.

Bibliography

  1. Hess, R.A., et al, (1997) A role for estrogens in the male reproductive system, Letter to Nature, 390, 509.
  2. Bancroft J. (1989) Human Sexuality and its Problems, Edinburgh: Churchill Livingstone.
  3. Rose, S., (1991) The Chemistry of Life, London: Penguin Books.
  4. Thomas, M., Barrett, J.S., Montgomery, D.H., (1994) Serum markers of bone metabolism in a group of transsexual patients receiving estrogen therapy, in GENDYS' 94, The Third International Gender Dysphoria Conference, Report, Belper: GENDYS Conferences.

NEXT Testosterone and Aggression.

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Citation
Bland, J.,(2003) About Gender: Estrogens and Androgens.
http://www.gender.org.uk/about/06encrn/62_hormn.htm
 
Book graphics courtesy of Amazon.co.uk
Web page copyright Derby TV/TS Group. Text copyright Jed Bland.
22.05.98 amended 10.07.99, 30.12.03