GnRH, more basic than "unspecified" ste2,3

Richard Aaron Warnock erawtech at leland.Stanford.EDU
Fri Mar 15 08:28:31 EST 1996

In article <Pine.ULT.3.91.960315014238.163B-100000 at essex.UCHSC.edu>,
Teresa Binstock  <binstoct at essex.UCHSC.edu> wrote:
>Teresa responds that her S/O and G/O hypothesis is alive and well for the 
>following reasons:
>0. Whether or not Patel et al's STE2 and STE3 are labeling molecules 
>homologous to S. cerevisiae STE2 and STE3 is not necessarily relevant. 

You started off based on this, now you discard it because you find you
don't know what it is. I think that's a bit relevent to your
reasoning, if not your proposal.

>1. Yeast's alpha-factor is functionally homologous to mammalian GnRH.

Nope. GnRH (gonadotropin releasing hormone) is not a/the homologue at
all. You noted how you could express heterologous genes from yeast in
mammalian cells and vice versa and show homologous function. Isn't the
case here. Not a bit. These GnRH are a family of neuropeptides
expressed widely throughout the body. You can treat mammalian cells
with a-factor and get a response, but what's the relevence? See more
below at #5.

>2. GnRH and GnRH receptors are in the thymus and are expressed on 
>T-cells; in other words, a mammalian functional-homologue of alpha-factor 
>is present in the thymus and in T-cells.

As above, a particular GnRH with the function of alpha-factor has not
been isolated. The receptor(s) for GnRH are widely expressed, not just
in the thymic environment. Your autoimmune theory gets really weak
when you first suppose that the antigen is expressed on T cells as
well as all over the body! So the auto-antigen driven autoimmunity is
systemic, now you've got more than sexual identity changes!

>3. Yeast's reception of alpha-factor affects cell cycle. At least one 
>study thus far reports that mammalian GnRH affects cell cycle in T cells. 

Yeah, so? How does this link to anything? 

>4. Just as one class of yeast cells generally produces GnRH-like 
>alpha-factor, so too do human T-cells produce GnRH.

Nope. This is not linked. T cells produce LHRH, but this is not the
same as yeast making alpha-factor. While they may both affect
reproduction, they are not the same functionally, nor physically at
the level of molecular mechanisms.

>5. Whether or not a-factor homologues exist in humans remains to be 
>reported; what is clear is that the basic structure of a-factor molecules 
>is quite similar to endogenous substances in humans.

Like what, and how is it relevent?

Even if a-factor activates gonadotrophs, so what?

>In general, therefore, the fact that GnRH-receptors exist in the 
>mammalian thymus indicates that molecules functionally akin to alpha-factor 
>receptors exist in the mammalian thymus -- totally independently of what 
>Patel et al were referring to via their use of the acronyms STE2 and STE3.

You've not shown that alpha-factor receptors are homologous to
anything! If you search the database, you'll find nothing even close
in mammalians! In order for your autoimmune theory to work, there must
be conserved structure, not just function (which isn't conserved
either anyway).

Your faulty logic is:
	alpha factor is similar to some GnRH.
	alpha factor and GnRH bind receptors.
	alpha factor receptor must be similar to some GnRH receptor.

This is simply not the case. Some receptors can bind many
substrates/counter-receptors, and some substrates can bind many
receptors. Clearly, a somewhat similar peptide across evolutionary
boundries, does not imply conserved receptor structure, much less
function. Thus, there is no evidence, *at all*, that there is
something similar to these alpha-factor receptors on thymic
epithelieum, or any other cell type of the thymus. And while alpha
factor peptides are homologous to some GnRH, they are different enough
to require significant changes in receptor structure of GnRH receptor.

>To move forwards, S. Cerevisiae has genes for both a- and alpha-factor 
>pheromones and receptors, but generally expresses and utilizes only the 
>appropriate pheromone and receptor combination. 

The following sentence contains several huge jumps in logic:

>Similarly, male and 
>female humans, amidst all their beyond-yeast complexity, have all the 
>GnRH-capabilities enumerated hereinabove, but also have a more complex 
>immune system than does S. Cerevisiae; thus (at least hypothetically) 
>humans have more diverse ways whereby sex-identification alternatives 
>(ie variations of sexual and/or gender orientation) could occur -- ie, 
>by mechanisms like those of autoimmumity, but focused in relation to 
>sexually significant chemo-signaling, as perceived in the nasal mucosa and 
>possibly the epidermis.

Your faulty logic:
	Yeast select mating partiners by a system.
	Humans have yeast homolgeous proteins.
	Humans must have similar mating signal systems.
	And a more complicated immune system.
	And these must be related in function.
	Disregulation of immune system results in disregulated mating.

I think if you just read your summary sentence, you'll see the problem:
	it doesn't flow logically.

>Cites in support of the numbered statements:

Your arguements would be stronger if you match and summerize your
cites at the appropriate part of your statements:


Rheumatoid arthritic models of disease involving innoculation or
rabbits with cartiledge, have shown a profound up-regulation of
P-selectin. Additionally, increased interaction of leukocytes is found
along the venous endothelium of inflammed synovium(jones, '92), in a
P-selectin dependent manner(smith, '92). Other models of chronic
inflammation, peritonitis, skin DTH, chronic rotavirus infection of
the gut, have not shown this (Brown, '93, Doe,'95 & Green '93
respectively)chronic expression of CD62-P. Thus, chronic, constituitve
expression of P-selectin at inflammed joints suggest the possibility
that CD62-P is a tissue-specific addressin in this context.

As it is, I believe you've simply printed a list of cites you read
abstracts/or titles of. You must explain how each point you make fits
a model, how your model explains the availible data (cites), and what
your model predicts. Otherwise, your reasoning hasn't really even made
it to shakey.

[cite list snipped]


"Nothing more is needed to destroy a man, than the conviction that his
life's work is useless."  -Antonin Artaud

erawtech at leland.stanford.edu (R. Aaron Warnock)

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